A Molecular Dynamics Approach for Pre-screening Computational Enzyme Design Results

BERNARDO SOSA PADILLA ARAUJO; THOMAS MILLER; STEPHEN MAYO

San Diego, California

Conferencia; The 24th Annual Symposium of The Protein Society; 2010

The Protein Society

Computational enzyme design is a very promising area of research. However, current computational design tools suffer from a serious limitation: they cannot reliably predict active sequences and thus produce a large number of false-positives. Consequently, investigators have had to rely on screening hundreds of designs in order to find a few active ones. In addition, both protein dynamics and explicit solvation are important aspects of enzyme function and are therefore critical to predicting enzymatic activity. Unfortunately, protein design methodology rarely takes these factors into account. Molecular dynamics (MD) simulations, on the other hand, can model both. We have developed a MD protocol that provides a reliable and computationally feasible way of pre-screening enzyme designs. Preliminary data have shown outstanding correlations with experimental results. We also have tested the generality of the methodology on a larger and more diverse set of enzymes for which experimental data already exists. The method is accurate, reproducible, and exhibits encouraging computational performance.