Prediction of loop geometries using a generalized born model of solvation effects

✍ Scribed by Chaya Sendrovic Rapp; Richard A. Friesner

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 350 KB
• Volume: 35
• Category: Article
• ISSN: 0887-3585
• DOI: 10.1002/(sici)1097-0134(19990501)35:2<173::aid-prot4>3.0.co;2-2

✦ Synopsis

We have carried out an extensive exploration of the possibility of predicting the structure of long loops in proteins, using an 8-and a 12-residue loop in ribonuclease A as models. The native X-ray structure is used as a template while allowing for template flexibility; this makes our work relevant to the problem of homology modeling in which the template is not precisely known. Energies are calculated with the AMBER* and AMBER94 molecular mechanics potentials and the generalized Born continuum solvation model; and conformational space is sampled by means of a combination of Monte Carlo and molecular dynamics methods. Our AMBER94 results demonstrate that we can successfully generate loops with low root-meansquare deviations from the native as well as excellent energetic rankings.