David Gohara, Ph.D.
Adjunct Assistant Professor
Biochemistry and Molecular Biology
Investigation of macromolecular structure/function relationships using computer based
Dynamics and Electrostatics
One of the biggest challenges in trying to understand how structure affects function is assessing energetic properties of macromolecules. In this regard, computational techniques can help provide insight into possible mechanisms of action. In many cases, these methods are complimentary to experimental methods and can be helpful in developing further experimentally testable hypotheses.
To the right are several simulations that were performed to better understand the roles that dynamics and electrostatics have in driving molecular interactions.
Conformational Sampling for Drug Discovery
A particularly interesting problem is generating conformational states that can then be used subsequently for in-silico docking. Molecular dynamics is a useful method for generating high probability cluster states. This is more important when only handful of structures are available for a given molecule. However, even in cases where a large number of structures are available, structural variation (in the dynamic sense) may not be as readily observed (although probably exist outside the static crystal structure).
One such example are the trypsin-like family of serine proteases (e.g., thrombin). The image gallery below illustrates the point (open the gallery to for more details).
My primary research these days focuses on the use of graphics processing units (GPUs) in scientific computations. Specifically the application of high performance computing for structural biology applications. Technologies such as CUDA, Stream and OpenCL have made accessing the processing power of the GPU much easier. OpenCL, an open specification, in particular, has been established as a standard for accessing not only GPUs but any hardware specific feature that possesses a programmable pipeline.
Costimulatory Effects of an Immunodominant Parasite Antigen Paradoxically Prevent
Induction of Optimal CD8 T Cell Protective Immunity
Eickhoff CS, Zhang X, Vasconcelos JR, Motz RG, Sullivan NL, O’Shea K, Pozzi N, Gohara DW, Blase JR, Di Cera E and Hoft DF
Pubmed | PLoS Pathog.
Loop Electrostatics Asymmetry Modulates the Preexisting Conformational Equilibrium
Pozzi N, Zerbetto M, Acquasaliente L, Tescari S, Frezzato D, Polimeno A, Gohara DW, Di Cera E and De Filippis V
Pubmed | Biochemistry
Potassium and the K+/H+ Exchanger Kha1p Promote Binding of Copper to ApoFet3p Multi-copper
Wu X, Kim H, Seravalli J, Barycki JJ, Hart PJ, Gohara DW, Di Cera E, Jung WH, Kosman DJ and Lee J
Pubmed | J. Biol. Chem.