From owner-chemistry@ccl.net Sun Jul 7 12:12:00 2013 From: "Andreas Bender, PhD Andreas.Bender_-_cantab.net" To: CCL Subject: CCL: Call for Papers - SLAS 2014 with 'Scientific Informatics' programme, San Diego, 18-22 January 2014 Message-Id: <-48895-130707120001-21563-d1pT6wPlW1fuAMkkHpDuiQ+/-server.ccl.net> X-Original-From: "Andreas Bender, PhD" Content-Type: text/plain; charset=ISO-8859-1 Date: Sun, 7 Jul 2013 16:59:53 +0100 MIME-Version: 1.0 Sent to CCL by: "Andreas Bender, PhD" [Andreas.Bender ~ cantab.net] Call for Papers 3rd Annual Conference of the Society for Laboratory Automation and Screening (Including a dedicated 'Scientific Informatics' programme comprising 24 talks in 6 sessions) 'SLAS2014' - http://www.slas2014.org/ San Diego Convention Center, San Diego, California 18 - 22 January 2014 Dear All, I would like to cordially invite you to 'SLAS2014', the 3rd Annual Conference of the Society for Laboratory Automation and Screening (SLAS), which will take place in San Diego/CA, from 18 - 22 January 2014 and which will feature a dedicated informatics track in this instance as well. Abstracts for oral presentations can be submitted from now until the deadline on 5 August, with poster submissions being accepted until 28 October. The website for submissions of abstracts can be found at this address: http://www.slas2014.org/presenters/callforabstracts.cfm . The SLAS is an international non-profit community of more than 15,000 individual scientists, engineers, researchers and technologists from academic, government and commercial laboratories, and provides forums for education and information exchange to encourage study and advance laboratory science and technology for life science R&D. The upcoming annual conference (San Diego, CA, USA, January 18-22, 2014) will feature 132 outstanding podium presentations comprising 33 unique scientific sessions, over 300 posters and new and emerging technologies from 300+ exhibitors from around the world. For those specifically interested Scientific Informatics, the podium program chaired by Scott Weiss (IDBS) will consist of 24 talks organized into the following sessions: - Pre-competitive and Collaborative Solutions to Common Problems - Chair: Dana Vanderwall - Data Mining in Chemical and Biological Spaces: If We Only Knew What We Knew? - Chair: Andreas Bender - Extracting Meaning from Complex Data - Chair: Ellen Berg - Converting Data to Knowledge - Chair: Art Morales - The Dynamic Lab: Informatics for Laboratory Operations Management - Chair: Mark Russo - Emerging Trends for Lab of the Future - Chair: Robin Smith Additionally, in other sessions you can preview scientific developments that are impacting informatics, such as: - Next Gen Sequencing - Cellular Assays - Droplet and Digital Microsystems - High Throughput Target Identification - Advances in High Throughput Analytics and Automation You are now very much invited to submit abstracts for oral presentations in the above (and other) sessions until 5 August at http://www.slas2014.org/presenters/callforabstracts.cfm ; the deadline for posters will be 28 October. If you have any particular queries please don't hesitate to let me know directly or any of the organizers listed above - looking forward to seeing you in San Diego in early 2014! Best wishes, Andreas -- Andreas Bender, PhD Lecturer for Molecular Informatics Unilever Centre, Cambridge University http://www-ucc.ch.cam.ac.uk Personal: http://www.andreasbender.de From owner-chemistry@ccl.net Sun Jul 7 12:46:00 2013 From: "Kshatresh Dutta Dubey kshatresh:+:gmail.com" To: CCL Subject: CCL: Comparison of Experimental and computational Binding Affinities Message-Id: <-48896-130707123022-29417-cKobmiCCY5LrWMnaphiI3g~~server.ccl.net> X-Original-From: Kshatresh Dutta Dubey Content-Type: multipart/alternative; boundary=001a11c2f7e66814b604e0ee71ed Date: Sun, 7 Jul 2013 22:00:16 +0530 MIME-Version: 1.0 Sent to CCL by: Kshatresh Dutta Dubey [kshatresh-$-gmail.com] --001a11c2f7e66814b604e0ee71ed Content-Type: text/plain; charset=ISO-8859-1 Dear All, I am very curious to know that whether the comparison of dissociation constant (Kd values) with computationally calculated free energy is valid or not. We often use DeltaG(binding)= -RTllnKd for this purpose. Suppose, I have two different drug-protein complexes A and B where the binding energy of A is more than B by 2.3 Kcal. This makes a difference of 50 fold in dissociation constant scale. Okay, it looks fine in the context of theory. However, in practical, if someone is using end point methods like MMPBSA or LIE to calculate the binding free energy for different complexes, they generally give error/difference of 4-5 kcal including entropy, that makes 100-200 fold differences in scale of Kd values. Now, my problem is that I have to compare affinity of five drugs having Kd values 1.6, 0.67, 10, 36 and 25 nM using MMPBSA/LIE methods. Is the comparison of binding affinity calculated by these methods(MMPBSA/LIE) in reference to Kd values possible? -- With best regards ******************************************************************************************************************* Kshatresh Dutta Dubey, PhD Post Doctoral Fellow Indian Institute of Technology Kanpur Kanpur, India --001a11c2f7e66814b604e0ee71ed Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable
Dear All,

=A0=A0 I am very curious to kn= ow that whether the comparison of dissociation constant (Kd values) with co= mputationally calculated free energy is valid or not. We often use DeltaG(b= inding)=3D -RTllnKd for this purpose. Suppose, I have two different drug-pr= otein complexes A and B where the binding energy of A is more than B by 2.3= Kcal. This makes a difference of 50 fold=A0 in dissociation constant scale= . Okay, it looks fine in the context of theory. However, in practical, if s= omeone is using end point methods like MMPBSA or LIE to calculate the bindi= ng free energy for different complexes, they generally give error/differenc= e of 4-5=A0 kcal including entropy, that makes 100-200 fold differences in = scale of Kd values.
=A0=A0 Now, my problem is that I have to compare affinity of five drugs hav= ing Kd values 1.6, 0.67, 10, 36 and 25 nM using MMPBSA/LIE methods. Is the = comparison of binding affinity calculated by these methods(MMPBSA/LIE) in r= eference to Kd values possible?=A0

--
With best regards
**************************************************************************= *****************************************
Kshatresh Dutta Dubey, PhD
Post Doctoral Fellow
Indian Institute of Technology Kanp= ur
Kanpur, India


--001a11c2f7e66814b604e0ee71ed-- From owner-chemistry@ccl.net Sun Jul 7 14:06:00 2013 From: "Hao-Bo Guo guohaobo::gmail.com" To: CCL Subject: CCL: Comparison of Experimental and computational Binding Affinities Message-Id: <-48897-130707130223-17852-srxlf36j4ks5FWNxgT1EGA]-[server.ccl.net> X-Original-From: Hao-Bo Guo Content-Type: multipart/alternative; boundary=047d7b2e0eebe4482604e0eee3d1 Date: Sun, 7 Jul 2013 13:02:16 -0400 MIME-Version: 1.0 Sent to CCL by: Hao-Bo Guo [guohaobo/a\gmail.com] --047d7b2e0eebe4482604e0eee3d1 Content-Type: text/plain; charset=ISO-8859-1 Dear Kshatresh, I have two points on this type of calculations: 1. The absolute values are always useless, and only the relative binding affinities or binding free energies are meaningful (owing to valuable error cancelation etc); and 2. You definitely need to systematically benchmark your method prior to the calculations. Good luck, Hao-Bo Guo On Sun, Jul 7, 2013 at 12:30 PM, Kshatresh Dutta Dubey kshatresh:+:gmail.com wrote: > Dear All, > > I am very curious to know that whether the comparison of dissociation > constant (Kd values) with computationally calculated free energy is valid > or not. We often use DeltaG(binding)= -RTllnKd for this purpose. Suppose, I > have two different drug-protein complexes A and B where the binding energy > of A is more than B by 2.3 Kcal. This makes a difference of 50 fold in > dissociation constant scale. Okay, it looks fine in the context of theory. > However, in practical, if someone is using end point methods like MMPBSA or > LIE to calculate the binding free energy for different complexes, they > generally give error/difference of 4-5 kcal including entropy, that makes > 100-200 fold differences in scale of Kd values. > Now, my problem is that I have to compare affinity of five drugs having > Kd values 1.6, 0.67, 10, 36 and 25 nM using MMPBSA/LIE methods. Is the > comparison of binding affinity calculated by these methods(MMPBSA/LIE) in > reference to Kd values possible? > > -- > With best regards > > ******************************************************************************************************************* > Kshatresh Dutta Dubey, PhD > Post Doctoral Fellow > Indian Institute of Technology Kanpur > Kanpur, India > > > --047d7b2e0eebe4482604e0eee3d1 Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable
Dear Kshatresh,

I have two points= on this type of calculations: 1. The absolute values are always useless, a= nd only the relative binding affinities or binding free energies are meanin= gful (owing to valuable error cancelation etc); and 2. You definitely need = to systematically benchmark your method prior to the calculations.

Good luck,
Hao-Bo Guo
=


On Sun,= Jul 7, 2013 at 12:30 PM, Kshatresh Dutta Dubey kshatresh:+:gmail.com <owner-chemistry[A]ccl.net> = wrote:
Dear All,

=A0=A0 I am very curious to know that whether the comparison of dissociati= on constant (Kd values) with computationally calculated free energy is vali= d or not. We often use DeltaG(binding)=3D -RTllnKd for this purpose. Suppos= e, I have two different drug-protein complexes A and B where the binding en= ergy of A is more than B by 2.3 Kcal. This makes a difference of 50 fold=A0= in dissociation constant scale. Okay, it looks fine in the context of theo= ry. However, in practical, if someone is using end point methods like MMPBS= A or LIE to calculate the binding free energy for different complexes, they= generally give error/difference of 4-5=A0 kcal including entropy, that mak= es 100-200 fold differences in scale of Kd values.
=A0=A0 Now, my problem is that I have to compare affinity of five drugs hav= ing Kd values 1.6, 0.67, 10, 36 and 25 nM using MMPBSA/LIE methods. Is the = comparison of binding affinity calculated by these methods(MMPBSA/LIE) in r= eference to Kd values possible?=A0

--
With best regards
**************************************************************************= *****************************************
Kshatresh Dutta Dubey, PhD
Post Doctoral Fellow
Indian Institute of Technology Kanp= ur
Kanpur, India



--047d7b2e0eebe4482604e0eee3d1-- From owner-chemistry@ccl.net Sun Jul 7 22:56:00 2013 From: "Kshatresh Dutta Dubey kshatresh{:}gmail.com" To: CCL Subject: CCL: Comparison of Experimental and computational Binding Affinities Message-Id: <-48898-130707150955-13310-e/YWEQeB5iJ00RmQUhXN2A^^^server.ccl.net> X-Original-From: Kshatresh Dutta Dubey Content-Type: multipart/alternative; boundary=e89a8f503b160bdc0c04e0f0acbf Date: Mon, 8 Jul 2013 00:39:50 +0530 MIME-Version: 1.0 Sent to CCL by: Kshatresh Dutta Dubey [kshatresh/a\gmail.com] --e89a8f503b160bdc0c04e0f0acbf Content-Type: text/plain; charset=ISO-8859-1 Dear Guo, Thanks for your reply. However, if I change 1.6nM, 0.6nM, 10 nM, in Kcal/mol using above formula, the difference in energy values are very small. But the results of MMPBSA show difference of almost 05-10 kcal/mol that means a large difference in kd values. So, can I compare the relative binding affinities of these drugs using MMPBSA? Thanks kdd On Sun, Jul 7, 2013 at 10:32 PM, Hao-Bo Guo guohaobo::gmail.com < owner-chemistry]=[ccl.net> wrote: > Dear Kshatresh, > > I have two points on this type of calculations: 1. The absolute values are > always useless, and only the relative binding affinities or binding free > energies are meaningful (owing to valuable error cancelation etc); and 2. > You definitely need to systematically benchmark your method prior to the > calculations. > > Good luck, > Hao-Bo Guo > > > On Sun, Jul 7, 2013 at 12:30 PM, Kshatresh Dutta Dubey kshatresh:+: > gmail.com wrote: > >> Dear All, >> >> I am very curious to know that whether the comparison of dissociation >> constant (Kd values) with computationally calculated free energy is valid >> or not. We often use DeltaG(binding)= -RTllnKd for this purpose. Suppose, I >> have two different drug-protein complexes A and B where the binding energy >> of A is more than B by 2.3 Kcal. This makes a difference of 50 fold in >> dissociation constant scale. Okay, it looks fine in the context of theory. >> However, in practical, if someone is using end point methods like MMPBSA or >> LIE to calculate the binding free energy for different complexes, they >> generally give error/difference of 4-5 kcal including entropy, that makes >> 100-200 fold differences in scale of Kd values. >> Now, my problem is that I have to compare affinity of five drugs >> having Kd values 1.6, 0.67, 10, 36 and 25 nM using MMPBSA/LIE methods. Is >> the comparison of binding affinity calculated by these methods(MMPBSA/LIE) >> in reference to Kd values possible? >> >> -- >> With best regards >> >> ******************************************************************************************************************* >> Kshatresh Dutta Dubey, PhD >> Post Doctoral Fellow >> Indian Institute of Technology Kanpur >> Kanpur, India >> >> >> > -- With best regards ******************************************************************************************************************* Kshatresh Dutta Dubey, PhD Post Doctoral Fellow Indian Institute of Technology Kanpur Kanpur, India --e89a8f503b160bdc0c04e0f0acbf Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable
Dear Guo,

Thanks for your reply. = However, if I change 1.6nM, 0.6nM, 10 nM, in Kcal/mol using above formula, = the difference in energy values are very small. But the results of MMPBSA s= how difference of almost 05-10 kcal/mol that means a large difference in kd= values. So, can I compare the relative binding affinities of these drugs u= sing MMPBSA?=A0

Thanks
kdd


On Sun, Jul 7, 201= 3 at 10:32 PM, Hao-Bo Guo guohaobo::gmail.com<= /a> <owner-chemistry]=[ccl.net> wrote:
Dear Kshatresh,

I have two points on this type of calculations: 1. The absolute val= ues are always useless, and only the relative binding affinities or binding= free energies are meaningful (owing to valuable error cancelation etc); an= d 2. You definitely need to systematically benchmark your method prior to t= he calculations.

Good luck,
Hao-Bo Guo


On Sun, Jul 7, 2013 at 12:30 PM, Kshatresh Dutta Dubey ksh= atresh:+:gmail.com <owner-chemistry:+:ccl.net> wrote:
Dear All,

=A0=A0 I am very curious to know that whether the comparison of dissociati= on constant (Kd values) with computationally calculated free energy is vali= d or not. We often use DeltaG(binding)=3D -RTllnKd for this purpose. Suppos= e, I have two different drug-protein complexes A and B where the binding en= ergy of A is more than B by 2.3 Kcal. This makes a difference of 50 fold=A0= in dissociation constant scale. Okay, it looks fine in the context of theo= ry. However, in practical, if someone is using end point methods like MMPBS= A or LIE to calculate the binding free energy for different complexes, they= generally give error/difference of 4-5=A0 kcal including entropy, that mak= es 100-200 fold differences in scale of Kd values.
=A0=A0 Now, my problem is that I have to compare affinity of five drugs hav= ing Kd values 1.6, 0.67, 10, 36 and 25 nM using MMPBSA/LIE methods. Is the = comparison of binding affinity calculated by these methods(MMPBSA/LIE) in r= eference to Kd values possible?=A0

--
With best regards
**************************************************************************= *****************************************
Kshatresh Dutta Dubey, PhD
Post Doctoral Fellow
Indian Institute of Technology Kanp= ur
Kanpur, India






--
=
With best regards
*************************= ***************************************************************************= ***************
Kshatresh Dutta Dubey, PhD
Post Doctoral Fellow
Ind= ian Institute of Technology Kanpur
Kanpur, India


<= /div>
--e89a8f503b160bdc0c04e0f0acbf--