SRC+Project

=Validation of Virtual Screening Methods=

10/1912 - Alex Hsu working on a virtual project through the Semiconductor Research fellowship

REVISED GOAL: 1/20/13
Figure out how to run a Virtual Screening Job on the AWS (Amazon Web Services) EC2 system using a linux virtual machine and VINA Write a protocol for setting up the system Write protocol for an end -user

Alex to get working on his free account - do a test dock of 30,000 ligands, create a Bestranking list and view top poses in PyMol. Generate a step-by-step protocol for this Then set it up in the VDS account and get it working there so that we can put the $400 amount from the URF (undergraduate research fellowship) there.

Amazon Web Services Notes (running notes for Alex and Dr. B to use):
@https://docs.google.com/document/d/1UT4D0rRKu1tKuAjjK9NorShrrSyOH-K9E1v56d7awZ4/edit?usp=sharing EC2 FAQ's: @http://aws.amazon.com/ec2/faqs/

Your AWS Account Alias is **vdsclass** IAM users sign-in link:
 * https://vdsclass.signin.aws.amazon.com/console**

GOAL:
Determine if Molecular Mechanics and/or Molecular Dynamics calculations improve the accuracy of ranking over regular virtual screening.

Specific Aims:
Find a good test system with which to validate (with positive and negative controls). - use GOLD test set (on the GOLD website at CCDC) - however, these may not have 'wet lab' data to compare to (e.g. IC50s, or Ki values that correlate to true FEB energies). - use other known binders to an example protein. Would need to have Ki, IC50 or deltaG info from ITC (Isothermal Titration Calorimetry) - include list of 'dummy' atoms and/or negative controls that we don't expect to bind

Use GOLD, ICM, VINA to carry out regular docking -- sa Use AMBER on TACC to carry out calculations

Compare ranking lists of VS vs MM/MD calcs

Maybe do some wet lab verification of results Maybe do a wet lab prospective study of novel ligands (do their wet lab binding affinities rank according to MM/MD calc rankings?)

REFERENCES & RESOURCES
AMBER site - @http://ambermd.org/ CHARM site

@http://pubs.acs.org/doi/full/10.1021/bi201449r
 * This paper has a section on molecular modeling using the QM/MM method (from the Fast lab at UT Austin)**

Denque research using TACC with Autodock and AMBER or CHARM for FEB (Free Energy of Binding) calculations
 * Watowich/Malmstrom papers:**