Connecting Quantum Mechanics to Molecular Dynamics: Generating a Ligand Topology

Poster Number

13B

Lead Author Major

Biochemistry

Lead Author Status

Senior

Format

Poster Presentation

Faculty Mentor Name

Mike McCallum

Faculty Mentor Department

Chemistry

Additional Faculty Mentor Name

Hyun Joo

Abstract/Artist Statement

A topology file provides the physical parameters necessary for Molecular Dynamic (MD) simulations. A topology file needs to be generated from a set of coordinates from Quantum Mechanical (QM) calculations. We used Gaussian to optimize and generate the classical charges for the ligand LDN, which is the first time the topology for this molecule has been calculated. After calculations are finished, rotations around non-chiral atoms can be made to possibly find more stable conformations that could be different than the given structure. Once a minimum is found a force-field topology file can then be constructed. This will be released for use by other scientists as part of the large dictionary of topology files for the CHARMM force-field. This means that other users will be able to use different sections of LDN’s topology for other molecules that have a similar structure. By having a ligand’s topology, we are able to better understand the factor that it’s charge plays into binding. The ability to run a MD simulation also gives us the ability to understand how the ligand possibly binds to the site and how we could improve the manufactured ligand. Having a large library of ligand topologies is very helpful in the field of drug discovery.

Location

DeRosa University Center Ballroom

Start Date

27-4-2018 12:30 PM

End Date

27-4-2018 2:30 PM

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Apr 27th, 12:30 PM Apr 27th, 2:30 PM

Connecting Quantum Mechanics to Molecular Dynamics: Generating a Ligand Topology

DeRosa University Center Ballroom

A topology file provides the physical parameters necessary for Molecular Dynamic (MD) simulations. A topology file needs to be generated from a set of coordinates from Quantum Mechanical (QM) calculations. We used Gaussian to optimize and generate the classical charges for the ligand LDN, which is the first time the topology for this molecule has been calculated. After calculations are finished, rotations around non-chiral atoms can be made to possibly find more stable conformations that could be different than the given structure. Once a minimum is found a force-field topology file can then be constructed. This will be released for use by other scientists as part of the large dictionary of topology files for the CHARMM force-field. This means that other users will be able to use different sections of LDN’s topology for other molecules that have a similar structure. By having a ligand’s topology, we are able to better understand the factor that it’s charge plays into binding. The ability to run a MD simulation also gives us the ability to understand how the ligand possibly binds to the site and how we could improve the manufactured ligand. Having a large library of ligand topologies is very helpful in the field of drug discovery.