2.1 and 1.8 A average C(alpha) RMSD structure predictions on two small proteins, HP-36 and s15

J Am Chem Soc. 2001 Feb 14;123(6):1040-6. doi: 10.1021/ja003150i.

Abstract

On two different small proteins, the 36-mer villin headpiece domain (HP-36) and the 65-mer structured region of ribosomal protein (S15), several model predictions from the ab initio approach Rosetta were subjected to molecular dynamics simulations for refinement. After clustering the resulting trajectories into conformational families, the average molecular mechanics--Poisson Boltzmann/surface area (MM-PBSA) free energies and alpha carbon (C(alpha)) RMSDs were then calculated for each family. Those conformational families with the lowest average free energies also contained the best C(alpha) RMSD structures (1.4 A for S15 and HP-36 core) and the lowest average C(alpha) RMSDs (1.8 A for S15, 2.1 A for HP-36 core). For comparison, control simulations starting with the two experimental structures were very stable, each consisting of a single conformational family, with an average C(alpha) RMSD of 1.3 A for S15 and 1.2 A for HP-36 core (1.9 A over all residues). In addition, the average free energies' ranks (Spearman rank, r(s)) correlate well with the average C(alpha) RMSDs (r(s) = 0.77 for HP-36, r(s) = 0.83 for S15). Molecular dynamics simulations combined with the MM--PBSA free energy function provide a potentially powerful tool for the protein structure prediction community in allowing for both high-resolution structural refinement and accurate ranking of model predictions. With all of the information that genomics is now providing, this methodology may allow for advances in going from sequence to structure.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Models, Molecular
  • Neurofilament Proteins / chemistry*
  • Peptide Fragments / chemistry*
  • Protein Conformation
  • Ribosomal Proteins / chemistry*

Substances

  • Neurofilament Proteins
  • Peptide Fragments
  • Ribosomal Proteins
  • ribosomal protein S15
  • villin headpiece subdomain peptide