Restriction versus guidance in protein structure prediction.
Conformational restriction by fragment assembly and guidance in molecular dynamics are alternate conformational search strategies in protein structure prediction. We examine both approaches using a version of the associative memory Hamiltonian that incorporates the influence of water-mediated interactions (AMW). For short proteins (<70 residues), fragment assembly, while searching a restricted space, compares well to molecular dynamics and is often sufficient to fold such proteins to near-native conformations (4A) via simulated annealing. Longer proteins encounter kinetic sampling limitations in fragment assembly not seen in molecular dynamics which generally samples more native-like conformations. We also present a fragment enriched version of the standard AMW energy function, AMW-FME, which incorporates the local sequence alignment derived fragment libraries from fragment assembly directly into the energy function. This energy function, in which fragment information acts as a guide not a restriction, is found by molecular dynamics to improve on both previous approaches.
Hegler
Joseph A
JA
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093-0365, USA.
Lätzer
Joachim
J
Shehu
Amarda
A
Clementi
Cecilia
C
Wolynes
Peter G
PG
D019295:Computational Biology / Q000379:methods*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*
D011506:Proteins
Proteins. 2007;69 Suppl 8:38-56
17894352
Curr Opin Struct Biol. 2004 Feb;14(1):70-5
15102452
Annu Rev Phys Chem. 1997;48:545-600
9348663
Protein Sci. 1996 Jun;5(6):1043-59
8762136
Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4918-22
1594594
Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1679-84
12554830
Biopolymers. 1983 Dec;22(12):2577-637
6667333
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19819-24
18077414
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3352-7
14988499
Adv Protein Chem. 2003;66:27-85
14631816
J Comput Chem. 2002 Jan 15;23(1):138-46
11913379
Proteins. 2009 Sep;76(4):837-51
19280604
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2025-30
10051588
Bioinformatics. 2003 Aug 12;19(12):1589-91
12912846
J Mol Biol. 1997 Apr 25;268(1):209-25
9149153
Science. 1989 Oct 20;246(4928):371-3
17747919
J Am Chem Soc. 2006 Apr 19;128(15):5168-76
16608353
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19825-30
18077415