http://www2.lut.fi/~jkamarai/misc/poster/latexhelp.html
http://www.swarthmore.edu/NatSci/cpurrin1//posteradvice.htm
I would say that in general, the posters that did the best were very clear and required little explanation. They had good leading headers above all figures, basically outlining in a few words what the figures showed. They had summaries or conclusions that were very clear, and it was clear from the verbal exchange what the presenter had contributed to the research and that the presenter was an expert in their field.
the Pimp My Poster group icon
Pimp My Poster
http://www.flickr.com/groups/688685@N24/
Sunday, April 5, 2009
Dr. Miller and Dr. Borchers
My two judges at the poster competition
http://www.pac.dfo-mpo.gc.ca/sci/mgl/staff_profiles/miller_e.htm#Area
Dr. Kristi Miller (Saunders)
Primary work on Marine Ecological Genomics and Adaptation Group (MEGA)
http://www.genomebc.ca/research_tech/researcher_profiles/c_borchers.htm
Dr. Christoph Borchers
Genome BC Platform Leader
Too bad I didn't win, but it was a good experience!
http://www.pac.dfo-mpo.gc.ca/sci/mgl/staff_profiles/miller_e.htm#Area
Dr. Kristi Miller (Saunders)
Primary work on Marine Ecological Genomics and Adaptation Group (MEGA)
http://www.genomebc.ca/research_tech/researcher_profiles/c_borchers.htm
Dr. Christoph Borchers
Genome BC Platform Leader
Too bad I didn't win, but it was a good experience!
Biomarkers
http://en.wikipedia.org/wiki/Biomarker
A biomarker is a substance used as an indicator of a biologic state. It is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.
It can also be a substance whose detection indicates a particular disease state, for example, the presence of an antibody may indicate an infection (see biomarker (medicine)). More specifically, a biomarker indicates a change in expression or state of a protein that correlates with the risk or progression of a disease, or with the susceptibility of the disease to a given treatment. Once a proposed biomarker has been validated, it can be used to diagnose disease risk, presence of disease in an individual, or to tailor treatments for the disease in an individual (choices of drug treatment or administration regimes). In evaluating potential drug therapies, a biomarker may be used as a surrogate for a natural endpoint such as survival or irreversible morbidity. If a treatment alters the biomarker, which has a direct connection to improved health, the biomarker serves as a surrogate endpoint for evaluating clinical benefit.
An NIH study group committed to the following definition in 1998: "a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention." [1]
In the past, biomarkers were primarily physiological indicators such as blood pressure or heart rate. More recently, biomarker is becoming a synonym for molecular biomarker, such as elevated prostate specific antigen as a molecular biomarker for prostate cancer, or using enzyme assays as liver function tests. Biomarkers also cover the use of molecular indicators of environmental exposure in epidemiologic studies such as human papilloma virus or certain markers of tobacco exposure such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
A biomarker is a substance used as an indicator of a biologic state. It is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.
It can also be a substance whose detection indicates a particular disease state, for example, the presence of an antibody may indicate an infection (see biomarker (medicine)). More specifically, a biomarker indicates a change in expression or state of a protein that correlates with the risk or progression of a disease, or with the susceptibility of the disease to a given treatment. Once a proposed biomarker has been validated, it can be used to diagnose disease risk, presence of disease in an individual, or to tailor treatments for the disease in an individual (choices of drug treatment or administration regimes). In evaluating potential drug therapies, a biomarker may be used as a surrogate for a natural endpoint such as survival or irreversible morbidity. If a treatment alters the biomarker, which has a direct connection to improved health, the biomarker serves as a surrogate endpoint for evaluating clinical benefit.
An NIH study group committed to the following definition in 1998: "a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention." [1]
In the past, biomarkers were primarily physiological indicators such as blood pressure or heart rate. More recently, biomarker is becoming a synonym for molecular biomarker, such as elevated prostate specific antigen as a molecular biomarker for prostate cancer, or using enzyme assays as liver function tests. Biomarkers also cover the use of molecular indicators of environmental exposure in epidemiologic studies such as human papilloma virus or certain markers of tobacco exposure such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
Wednesday, April 1, 2009
Immunology
- b-cells (bone marrow) has antibodies that bind antigens, then it makes clones of these b-cell types and the clones secrete antibodies into the blood stream, eg IgG, IgM (pentamer) (Y structure)
- t-cells 'killer' (thymus) has t-cell receptors which also has immnuglobulin (antibody) folds that recognizes antigens that are bound to mhc complex of infected cells (U structure only)
IgG (humoral, B-cell antibodies):
- immunoglobulin fold has 4 chains, 2 light and 2 heavy chains, 2 anti-parallel beta sheets packed against each other forming a barrel
- fc = crystalizable fragment, fab - antigen binding fragment
- fc and fab connected together by hinge region / flexible linker
- constant domain (ch1, cl) - 4+3 beta strand connected by short loops, linked by disulfide bonds, sheets are 90 degrees, hydrophobic interactions, 4 strands (longest sheet) in the middle, 3 strands in the outside
- variable domain (vh and vl) - 4+3+2 beta strand, long loops for antigen binding, cdr1-3 (complementarityy determining region) or hypervariable region on the same side, c' and c'' forms cdr2, cdr1 connects sheet 1 and 2 (crossover turn), cdr3 has the most variability, 5 strands in the middle (longest sheet) and 4 strands on the outside, c" not involved in packing (outside the barrel)
- epitope (Antigenic determinants) - part of antigen recognized by antibody (vs paratope - part of antibody recognize epitope)
T-Cell Receptors:
- t-cells 'killer' (thymus) has t-cell receptors which also has immnuglobulin (antibody) folds that recognizes antigens that are bound to mhc complex of infected cells (U structure only)
IgG (humoral, B-cell antibodies):
- immunoglobulin fold has 4 chains, 2 light and 2 heavy chains, 2 anti-parallel beta sheets packed against each other forming a barrel
- fc = crystalizable fragment, fab - antigen binding fragment
- fc and fab connected together by hinge region / flexible linker
- constant domain (ch1, cl) - 4+3 beta strand connected by short loops, linked by disulfide bonds, sheets are 90 degrees, hydrophobic interactions, 4 strands (longest sheet) in the middle, 3 strands in the outside
- variable domain (vh and vl) - 4+3+2 beta strand, long loops for antigen binding, cdr1-3 (complementarityy determining region) or hypervariable region on the same side, c' and c'' forms cdr2, cdr1 connects sheet 1 and 2 (crossover turn), cdr3 has the most variability, 5 strands in the middle (longest sheet) and 4 strands on the outside, c" not involved in packing (outside the barrel)
- epitope (Antigenic determinants) - part of antigen recognized by antibody (vs paratope - part of antibody recognize epitope)
T-Cell Receptors:
Protein crystallography
crystallography
- shine x-ray (1.5A = 1x10^-10 wavelength) on crystals (protein + h2o)
- treat reflections as summation waves (constructive interference = intensity)
- Bragg's Law: n(x-ray wavelength) = 2dsin(theta), d=lattice plane separation distance=resolution, theta is the incidence=reflection angle bouncing off the lattice plane, n=integral number of wavelengths in path length (extra distance travelled by beam on the 2nd lattice plane)
- structure factors (F) - wave equations that describe the reflections
- recombine structure factors to get an image of the molecular structure in the unit cell
- fourier transform - transforms reflections (diffraction patterns in reciprocal space) to electron density function in real space (and vice-versa)
- need to measure intensity and position (+ angle of reflection) of dots (miller indices hkl - name of reflections) in diffraction patterns, not errors (sigma)
- large unit crystals (proteins) produce reflections closer together (inverse relationship of theta and d in Bragg's Law)
- For a unit cell edge of 40 Å, and data collected to 2 Å resolution (d spacing)
40/2 = 20 planes = 20 spots along that direction
- For a unit cell edge of 80 Å, you now have 40 spots in the"same space"
so the reflections are twice as close together
- "as cell gets bigger, diffraction info is more + more compressed"
- phase problem - phase information is lost in the experiment, work arounds:
- MAD (multiple anomalous dispersion) - use SeMet, estimate Se atom phase from difference in Friedel mates, need to collect lots of data to find extent of error
- MIR (multiple isomorphous replacement) - soak crystals in heavy atoms (HA) while keeping the protein (P) isomorphic (same form), then we take the difference in structure factors, F(HA+P) - F(HA) = F(P), distance shown in Patterson map
- MR (molecular replacement) - homology, need at least 35% sequence identity, performs rotational and translational operations to match model with unknown
Methods for phase improvement:
- solvent flattening - ignore solvent envelope from e- density and mask it out
- histogram matching
- non-crystallographic symmetry (NCS) averaging
- shine x-ray (1.5A = 1x10^-10 wavelength) on crystals (protein + h2o)
- treat reflections as summation waves (constructive interference = intensity)
- Bragg's Law: n(x-ray wavelength) = 2dsin(theta), d=lattice plane separation distance=resolution, theta is the incidence=reflection angle bouncing off the lattice plane, n=integral number of wavelengths in path length (extra distance travelled by beam on the 2nd lattice plane)
- structure factors (F) - wave equations that describe the reflections
- recombine structure factors to get an image of the molecular structure in the unit cell
- fourier transform - transforms reflections (diffraction patterns in reciprocal space) to electron density function in real space (and vice-versa)
- need to measure intensity and position (+ angle of reflection) of dots (miller indices hkl - name of reflections) in diffraction patterns, not errors (sigma)
- large unit crystals (proteins) produce reflections closer together (inverse relationship of theta and d in Bragg's Law)
- For a unit cell edge of 40 Å, and data collected to 2 Å resolution (d spacing)
40/2 = 20 planes = 20 spots along that direction
- For a unit cell edge of 80 Å, you now have 40 spots in the"same space"
so the reflections are twice as close together
- "as cell gets bigger, diffraction info is more + more compressed"
- phase problem - phase information is lost in the experiment, work arounds:
- MAD (multiple anomalous dispersion) - use SeMet, estimate Se atom phase from difference in Friedel mates, need to collect lots of data to find extent of error
- MIR (multiple isomorphous replacement) - soak crystals in heavy atoms (HA) while keeping the protein (P) isomorphic (same form), then we take the difference in structure factors, F(HA+P) - F(HA) = F(P), distance shown in Patterson map
- MR (molecular replacement) - homology, need at least 35% sequence identity, performs rotational and translational operations to match model with unknown
Methods for phase improvement:
- solvent flattening - ignore solvent envelope from e- density and mask it out
- histogram matching
- non-crystallographic symmetry (NCS) averaging
Monday, March 30, 2009
scavenger hunt
Did some scavenger hunt on campus wih the club, about 12 ppl, 6 groups, 2 ppl each with an escort.
came down on 2nd place, just barely missed one riddle, if we only moved forward a bit more .... so close!
came down on 2nd place, just barely missed one riddle, if we only moved forward a bit more .... so close!
〜ね isn't it?
”ね”(ne) goes at the END of a sentence
これはいいですね。[kore ha ii desu ne.] [ex #698]
Isn't this nice !
ええと、映画館は駅の近くにありますね。[eeto, eigakan ha eki no chikaku ni arimasune.] [ex #699]
Er, the cinema is near the station, right?
これはいいですね。[kore ha ii desu ne.] [ex #698]
Isn't this nice !
ええと、映画館は駅の近くにありますね。[eeto, eigakan ha eki no chikaku ni arimasune.] [ex #699]
Er, the cinema is near the station, right?
Wednesday, March 25, 2009
風 (ふう) (みたい) ??? style
This also means wind ...
# 日本風のマンションでいいです。 [ex #710]
A Japanese style apartment is fine.
# たまにタイ風焼きうどんを食べます。 [ex #4787]
I sometimes eat Thai-style stir-fried noodles.
# 露天風呂のある純和風旅館に泊まった。 [ex #4788]
We stayed at a purely Japanese-style hotel with an open-air bath.
# どんな風に卵を作れますか？ [ex #5523]
In what kind of style can you cook eggs?
右 migi right
左 hidari left
昨日 kinou yesterday
明日 ashita tomorrow
本日 honjitsu today
来週 raishuu next week
食べる taberu eat
飲む nomu drink
書く kaku write
悪い warui bad
良い yoi good
新しい atarashi new
安 an relax
空の下 sora no shita Under the sky
空の上 sora no ue Above the sky
員 イン in employee
駅 エキ eki station
馬 うま uma horse
引 hiki pull
危 キ ki dangerous
過 カ ka excess, past
簡 カン kan simple
不 ふ fu negative
可 カ ka can
Pattern: subject (彼女 kanojo) wa, with (Tommy トミー) to, time ni, transportation (車 kuruma ) de, destination (駅 eki) ni, verb (itakimasu)
彼女はトミーとの駅まで車で行った ???
kanojo ha tomi^ to no eki made kuruma de itta
she went to the station with Tommy by car
# 日本風のマンションでいいです。 [ex #710]
A Japanese style apartment is fine.
# たまにタイ風焼きうどんを食べます。 [ex #4787]
I sometimes eat Thai-style stir-fried noodles.
# 露天風呂のある純和風旅館に泊まった。 [ex #4788]
We stayed at a purely Japanese-style hotel with an open-air bath.
# どんな風に卵を作れますか？ [ex #5523]
In what kind of style can you cook eggs?
右 migi right
左 hidari left
昨日 kinou yesterday
明日 ashita tomorrow
本日 honjitsu today
来週 raishuu next week
食べる taberu eat
飲む nomu drink
書く kaku write
悪い warui bad
良い yoi good
新しい atarashi new
安 an relax
空の下 sora no shita Under the sky
空の上 sora no ue Above the sky
員 イン in employee
駅 エキ eki station
馬 うま uma horse
引 hiki pull
危 キ ki dangerous
過 カ ka excess, past
簡 カン kan simple
不 ふ fu negative
可 カ ka can
Pattern: subject (彼女 kanojo) wa, with (Tommy トミー) to, time ni, transportation (車 kuruma ) de, destination (駅 eki) ni, verb (itakimasu)
彼女はトミーとの駅まで車で行った ???
kanojo ha tomi^ to no eki made kuruma de itta
she went to the station with Tommy by car
Monday, March 23, 2009
eee pc optimizations
1. Circular Scrolling
all you need to do is edit your /etc/X11/xorg.conf file
under "Input Device" of your touchpad edit to look like the following:
Section "InputDevice"
Identifier "Synaptics Touchpad"
Driver "synaptics"
Option "SendCoreEvents" "true"
Option "Device" "/dev/psaux"
Option "Protocol" "auto-dev"
Option "CircularScrolling" "1"
Option "Emulate3Buttons" "true"
Option "SHMConfig" "true"
EndSection
in firefox
mousewheel.horizscroll.withnokey.action - Set this to '1'
mousewheel.horizscroll.withnokey.numlines - Set this to '1'
http://wiki.eeeuser.com/howto:touchpad_in_advanced
run 'gsynaptics'
2. Firefox addons:
Download plug-ins for Firefox designed for compact computers and easier navigation. Some names to look for include: "Grab and Drag" and the theme "Tiny Menu."
https://addons.mozilla.org/en-US/firefox/addon/1250
https://addons.mozilla.org/en-US/firefox/addon/1455
3. Use RAMDISK in FireFox (check internet connection)
It turns out that there is a hidden setting in firefox called browser.cache.disk.parent_directory and all you need to do is set it's value to /dev/shm and restart firefox and then you are on your way to speedier surfing. so how do you set this, well it is simple
1) open firefox and type about:config in the address bar
2) accept the terms and click the "i'll be carefull" button
3) right click on any of the values on the screen to bring up the context menu and click new->string
4) the first prompt wants the name of the string enter "browser.cache.disk.parent_directory" without the quotes
5) the next prompt is the value set it to "/dev/shm/" without the quotes
6) restart firefox
7) type about:cache in the browser bar and it should tell you it is using /dev/shm under "Disk Cache Device" if you don't see a "Disk Cache Device" section you did something wrong.
4. Disable LAN and Webcam in the BIOS (Hit F2 upon starting the system) if these are not in use.
5. http://wiki.eeeuser.com/howto:maximize_screen_space
6. *some* of the boot process splash screens can be tweaked straight 'out of the box' via Control Center > Display > Theme > Splash Screen.
7. eee pc restore
http://sourceforge.net/project/showfiles.php?group_id=215613
http://www.glenscott.net/2008/11/12/restore-an-eee-pc-701-back-to-factory-xandros-from-a-usb-stick-with-no-asus-support-dvd/
8. flashplayer 10
http://forum.eeeuser.com/viewtopic.php?id=48308
http://download.macromedia.com/pub/labs/flashplayer10/flashplayer10_install_linux_081108.tar.gz
***********************************************
http://gadgetmix.com/index/?p=4102
http://forum.eeebuntu.org/viewtopic.php?t=294&reeedirected=yes
A lot of us have switched to EEEbuntu on our EEE PCs. If you are like me, who likes to keep his netbook clutter free, you will want to set up RAMdisk. And if you thought that setting up RAMdisk in Windows XP was easy (see this article), then in EEEbuntu, it is even easier.
* RAMdisk is located at “/dev/shm”
* Open firefox and type in about:config in the address bar
* Click on “I’ll be careful”
* make a new string browser.cache.disk.parent_directory
* give it a value /dev/shm
* restart firefox
Usual warning about RAMdisk: you will loose all the data upon restart. That is why, it is only recommended for web browsers
http://www.answerbag.com/articles/How-to-Optimize-an-ASUS-EEE-PC/aee034bf-bbb7-73f7-bb6b-826e0204caa0
http://www.callum-macdonald.com/2007/08/24/circular-scrolling/
For the techies, here’s the relevant section of my xorg.conf (see man synaptics for more info):
Section "ServerLayout"
Identifier "Default Server Layout"
Screen "Default Screen"
InputDevice "Generic Keyboard" "Core Keyboard"
InputDevice "Synaptics Touchpad" "Core Pointer"
EndSection
Section "InputDevice"
Identifier "Synaptics Touchpad"
Driver "synaptics"
Option "SendCoreEvents" "true"
Option "Device" "/dev/input/mice"
Option "Protocol" "auto-dev"
Option "CircularScrolling" "1"
Option "Emulate3Buttons" "true"
Option "SHMConfig" "true"
EndSection
Section "Extensions"
Option "Composite" "Enable"
EndSection
all you need to do is edit your /etc/X11/xorg.conf file
under "Input Device" of your touchpad edit to look like the following:
Section "InputDevice"
Identifier "Synaptics Touchpad"
Driver "synaptics"
Option "SendCoreEvents" "true"
Option "Device" "/dev/psaux"
Option "Protocol" "auto-dev"
Option "CircularScrolling" "1"
Option "Emulate3Buttons" "true"
Option "SHMConfig" "true"
EndSection
in firefox
mousewheel.horizscroll.withnokey.action - Set this to '1'
mousewheel.horizscroll.withnokey.numlines - Set this to '1'
http://wiki.eeeuser.com/howto:touchpad_in_advanced
run 'gsynaptics'
2. Firefox addons:
Download plug-ins for Firefox designed for compact computers and easier navigation. Some names to look for include: "Grab and Drag" and the theme "Tiny Menu."
https://addons.mozilla.org/en-US/firefox/addon/1250
https://addons.mozilla.org/en-US/firefox/addon/1455
3. Use RAMDISK in FireFox (check internet connection)
It turns out that there is a hidden setting in firefox called browser.cache.disk.parent_directory and all you need to do is set it's value to /dev/shm and restart firefox and then you are on your way to speedier surfing. so how do you set this, well it is simple
1) open firefox and type about:config in the address bar
2) accept the terms and click the "i'll be carefull" button
3) right click on any of the values on the screen to bring up the context menu and click new->string
4) the first prompt wants the name of the string enter "browser.cache.disk.parent_directory" without the quotes
5) the next prompt is the value set it to "/dev/shm/" without the quotes
6) restart firefox
7) type about:cache in the browser bar and it should tell you it is using /dev/shm under "Disk Cache Device" if you don't see a "Disk Cache Device" section you did something wrong.
4. Disable LAN and Webcam in the BIOS (Hit F2 upon starting the system) if these are not in use.
5. http://wiki.eeeuser.com/howto:maximize_screen_space
6. *some* of the boot process splash screens can be tweaked straight 'out of the box' via Control Center > Display > Theme > Splash Screen.
7. eee pc restore
http://sourceforge.net/project/showfiles.php?group_id=215613
http://www.glenscott.net/2008/11/12/restore-an-eee-pc-701-back-to-factory-xandros-from-a-usb-stick-with-no-asus-support-dvd/
8. flashplayer 10
http://forum.eeeuser.com/viewtopic.php?id=48308
http://download.macromedia.com/pub/labs/flashplayer10/flashplayer10_install_linux_081108.tar.gz
***********************************************
http://gadgetmix.com/index/?p=4102
http://forum.eeebuntu.org/viewtopic.php?t=294&reeedirected=yes
A lot of us have switched to EEEbuntu on our EEE PCs. If you are like me, who likes to keep his netbook clutter free, you will want to set up RAMdisk. And if you thought that setting up RAMdisk in Windows XP was easy (see this article), then in EEEbuntu, it is even easier.
* RAMdisk is located at “/dev/shm”
* Open firefox and type in about:config in the address bar
* Click on “I’ll be careful”
* make a new string browser.cache.disk.parent_directory
* give it a value /dev/shm
* restart firefox
Usual warning about RAMdisk: you will loose all the data upon restart. That is why, it is only recommended for web browsers
http://www.answerbag.com/articles/How-to-Optimize-an-ASUS-EEE-PC/aee034bf-bbb7-73f7-bb6b-826e0204caa0
http://www.callum-macdonald.com/2007/08/24/circular-scrolling/
For the techies, here’s the relevant section of my xorg.conf (see man synaptics for more info):
Section "ServerLayout"
Identifier "Default Server Layout"
Screen "Default Screen"
InputDevice "Generic Keyboard" "Core Keyboard"
InputDevice "Synaptics Touchpad" "Core Pointer"
EndSection
Section "InputDevice"
Identifier "Synaptics Touchpad"
Driver "synaptics"
Option "SendCoreEvents" "true"
Option "Device" "/dev/input/mice"
Option "Protocol" "auto-dev"
Option "CircularScrolling" "1"
Option "Emulate3Buttons" "true"
Option "SHMConfig" "true"
EndSection
Section "Extensions"
Option "Composite" "Enable"
EndSection
たい - I want
# 日本に行きたいです。 [ex #6442] (nippon ni iki taidesu)
(I) want to go to Japan.
# 君のところへ行きたいよ。 [ex #6458] (kun notokorohe iki taiyo)
(I) want to go to where you are.
# 日本で英語をおしえたいです。 [ex #6671] (nippon de eigo wooshietaidesu)
I want to teach English in Japan.
金 kin gold
魚 [さかな] (n) fish [K] [D]
(I) want to go to Japan.
# 君のところへ行きたいよ。 [ex #6458] (kun notokorohe iki taiyo)
(I) want to go to where you are.
# 日本で英語をおしえたいです。 [ex #6671] (nippon de eigo wooshietaidesu)
I want to teach English in Japan.
金 kin gold
魚 [さかな] (n) fish [K] [D]
Wednesday, March 18, 2009
Protein translocation and translation
Protein translocation and translation, signal peptidase complex (spc), ribosome,
http://www.rockefeller.edu/pubinfo/proteintarget.html
http://www.rockefeller.edu/pubinfo/proteintarget.html
Sunday, March 15, 2009
Mechanistic Basis of Enzyme-Targeted Drugs
Most often, subtle changes occur in the side
chain and main chain positions of the enzyme in order to
bind the substrates transition state optimally.
(Pauling).
http://pubs.acs.org/doi/full/10.1021/bi050247e
James G. Robertson*
Softzymics, Inc., Princeton, New Jersey 08540
Biochemistry, 2005, 44 (15), pp 5561–5571
DOI: 10.1021/bi050247e
Publication Date (Web): March 22, 2005
Some interesting paragraphs from the paper ...
Thus, it should be stated again. Enzymes are catalysts,
and the catalytic event is at least as important if not more
important than the binding event. Enzyme catalysis progresses
through binding events, conformational changes, one or more
transition states, or reaction intermediates, and product
release, and all of these steps occur with defined rate
constants. The rate constants define a thermodynamic profile
that can be used for drug design, and this differentiates
enzymes from all other target classes.
the larger the increase in replication time, the more toxic the drug
In
addition, purely kinetic information can be used to predict
potential drug toxicity. As an example, a detailed pre-steady-
state kinetic analysis of human mitochondrial DNA poly-
merase has been used to predict the potential toxicity of
marketed antiviral drugs.
One
of the major lessons to be learned from marketed drugs is
that nature has designed enzymes to perform a selective
chemical reaction, and therefore, it is likely that the most
potent drugs to be discovered or designed will be related to
the substrate structure, reactivity, or electrostatic potential
surface of intermediate(s) or transition state(s).
chain and main chain positions of the enzyme in order to
bind the substrates transition state optimally.
(Pauling).
http://pubs.acs.org/doi/full/10.1021/bi050247e
James G. Robertson*
Softzymics, Inc., Princeton, New Jersey 08540
Biochemistry, 2005, 44 (15), pp 5561–5571
DOI: 10.1021/bi050247e
Publication Date (Web): March 22, 2005
Some interesting paragraphs from the paper ...
Thus, it should be stated again. Enzymes are catalysts,
and the catalytic event is at least as important if not more
important than the binding event. Enzyme catalysis progresses
through binding events, conformational changes, one or more
transition states, or reaction intermediates, and product
release, and all of these steps occur with defined rate
constants. The rate constants define a thermodynamic profile
that can be used for drug design, and this differentiates
enzymes from all other target classes.
the larger the increase in replication time, the more toxic the drug
In
addition, purely kinetic information can be used to predict
potential drug toxicity. As an example, a detailed pre-steady-
state kinetic analysis of human mitochondrial DNA poly-
merase has been used to predict the potential toxicity of
marketed antiviral drugs.
One
of the major lessons to be learned from marketed drugs is
that nature has designed enzymes to perform a selective
chemical reaction, and therefore, it is likely that the most
potent drugs to be discovered or designed will be related to
the substrate structure, reactivity, or electrostatic potential
surface of intermediate(s) or transition state(s).
Subscribe to:
Posts (Atom)