TY - JOUR

T1 - Protein structure prediction using a combination of sequence homology and global energy minimization

T2 - II. Energy functions

AU - Dudek, Michael J.

AU - Ramnarayan, K.

AU - Ponder, Jay W.

PY - 1998/4/15

Y1 - 1998/4/15

N2 - A protein energy surface is constructed. Validation is through applications of global energy minimization to surface loops of protein crystal structures. For 9 of 10 predictions, the native backbone conformation is identified correctly. Electrostatic energy is modeled as a pairwise sum of interactions between anisotropic atomic charge densities. Model repulsion energy has a softness similar to that seen in ab initio data. Intrinsic torsional energy is modeled as a sum over pairs of adjacent torsion angles of 2-dimensional Fourier series. Hydrophobic energy is that of a hydration shell model. The remainder of hydration free energy is obtained as the energetic effect of a continuous dielectric medium. Parameters are adjusted to reproduce the following data: a complete set of ab initio energy surfaces, meaning one for each pair of adjacent torsion angles of each blocked amino acid; experimental crystal structures and sublimation energies for nine model compounds; ab initio energies over 1014 conformations of 15 small-molecule dimers; and experimental hydration free energies for 48 model compounds. All ab initio data is at the Hartree-Fock/6-31G* level.

AB - A protein energy surface is constructed. Validation is through applications of global energy minimization to surface loops of protein crystal structures. For 9 of 10 predictions, the native backbone conformation is identified correctly. Electrostatic energy is modeled as a pairwise sum of interactions between anisotropic atomic charge densities. Model repulsion energy has a softness similar to that seen in ab initio data. Intrinsic torsional energy is modeled as a sum over pairs of adjacent torsion angles of 2-dimensional Fourier series. Hydrophobic energy is that of a hydration shell model. The remainder of hydration free energy is obtained as the energetic effect of a continuous dielectric medium. Parameters are adjusted to reproduce the following data: a complete set of ab initio energy surfaces, meaning one for each pair of adjacent torsion angles of each blocked amino acid; experimental crystal structures and sublimation energies for nine model compounds; ab initio energies over 1014 conformations of 15 small-molecule dimers; and experimental hydration free energies for 48 model compounds. All ab initio data is at the Hartree-Fock/6-31G* level.

KW - Atomic multipoles

KW - Energy functions

KW - Global energy minimization

KW - Hydration free energy

KW - Structure prediction

KW - Surface loops

UR - http://www.scopus.com/inward/record.url?scp=0002067212&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1096-987X(19980415)19:5<548::AID-JCC7>3.0.CO;2-M

DO - 10.1002/(SICI)1096-987X(19980415)19:5<548::AID-JCC7>3.0.CO;2-M

M3 - Article

AN - SCOPUS:0002067212

SN - 0192-8651

VL - 19

SP - 548

EP - 573

JO - Journal of Computational Chemistry

JF - Journal of Computational Chemistry

IS - 5

ER -