The generalized molecular fractionation with conjugate caps/molecular mechanics method for direct calculation of protein energy.

A generalized molecular fractionation with conjugate caps/molecular mechanics (GMFCC/MM) scheme is developed for efficient linear-scaling quantum mechanical calculation of protein energy. In this GMFCC/MM scheme, the interaction energy between neighboring residues as well as between non-neighboring residues that are spatially in close contact are computed by quantum mechanics while the rest of the interaction energy is computed by molecular mechanics. Numerical studies are carried out to calculate torsional energies of six polypeptides using the GMFCC/MM approach and the energies are shown to be in general good agreement with the full system quantum calculation. Among those we tested is a polypeptide containing 396 atoms whose energies are computed at the MP26-31G* level. Our study shows that using GMFCC/MM, it is possible to perform high level ab initio calculation such as MP2 for applications such as structural optimization of protein complex and molecular dynamics simulation.

[1]  John Z. H. Zhang,et al.  Molecular fractionation with conjugate caps for full quantum mechanical calculation of protein-molecule interaction energy , 2003 .

[2]  D. York,et al.  Linear‐scaling semiempirical quantum calculations for macromolecules , 1996 .

[3]  Yutaka Akiyama,et al.  Fragment molecular orbital method: application to polypeptides , 2000 .

[4]  Wei Li,et al.  An efficient fragment-based approach for predicting the ground-state energies and structures of large molecules. , 2005, Journal of the American Chemical Society.

[5]  Kazuo Kitaura,et al.  On the accuracy of the 3-body fragment molecular orbital method (FMO) applied to density functional theory , 2004 .

[6]  S. Goedecker.  Linear scaling electronic structure methods , 1999 .

[7]  J. H. Zhang,et al.  Treating hydrogen bonding in ab initio calculation of biopolymers , 2006 .

[8]  Kenneth M. Merz,et al.  Quantum mechanical/quantum mechanical methods. I. A divide and conquer strategy for solving the Schrödinger equation for large molecular systems using a composite density functional–semiempirical Hamiltonian , 2000 .

[9]  John Z H Zhang,et al.  Quantum mechanical map for protein-ligand binding with application to beta-trypsin/benzamidine complex. , 2004, The Journal of chemical physics.

[10]  John Z H Zhang,et al.  An efficient approach for ab initio energy calculation of biopolymers. , 2005, The Journal of chemical physics.

[11]  Wei Li,et al.  Divide-and-conquer local correlation approach to the correlation energy of large molecules. , 2004, The Journal of chemical physics.

[12]  Y. Mo,et al.  New insight on the origin of the unusual acidity of Meldrum's acid from ab initio and combined QM/MM simulation study. , 2001, Journal of the American Chemical Society.

[13]  Kenneth M. Merz,et al.  Fully Quantum Mechanical Description of Proteins in Solution. Combining Linear Scaling Quantum Mechanical Methodologies with the Poisson−Boltzmann Equation , 1999 .

[14]  Yuto Komeiji,et al.  Fragment molecular orbital method: analytical energy gradients , 2001 .

[15]  S. L. Dixon,et al.  Semiempirical molecular orbital calculations with linear system size scaling , 1996 .

[16]  Yang,et al.  Direct calculation of electron density in density-functional theory. , 1991, Physical review letters.

[17]  C. Carter,et al.  Active Species for the Ground-State Complex of Cytidine Deaminase: A Linear-Scaling Quantum Mechanical Investigation , 1998 .

[18]  Yingkai Zhang,et al.  An efficient linear scaling method for ab initio calculation of electron density of proteins , 2004 .

[19]  John Z. H. Zhang,et al.  Fully quantum mechanical energy optimization for protein–ligand structure , 2004, J. Comput. Chem..

[20]  Paul G. Mezey,et al.  Ab Initio-Quality Electrostatic Potentials for Proteins: An Application of the ADMA Approach , 2002 .

[21]  X. Chen,et al.  Fractionation of peptide with disulfide bond for quantum mechanical calculation of interaction energy with molecules. , 2004, The Journal of chemical physics.

[22]  Weitao Yang,et al.  A density‐matrix divide‐and‐conquer approach for electronic structure calculations of large molecules , 1995 .

[23]  Peter A. Kollman,et al.  AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules , 1995 .

[24]  John Z H Zhang,et al.  Theoretical method for full ab initio calculation of DNA/RNA-ligand interaction energy. , 2004, The Journal of chemical physics.

[25]  John Z H Zhang,et al.  New Advance in Computational Chemistry:  Full Quantum Mechanical ab Initio Computation of Streptavidin-Biotin Interaction Energy. , 2003, The journal of physical chemistry. B.

[26]  Gustavo E. Scuseria,et al.  Semiempirical methods with conjugate gradient density matrix search to replace diagonalization for molecular systems containing thousands of atoms , 1997 .

[27]  D. Truhlar,et al.  Quantum Dynamics of Hydride Transfer in Enzyme Catalysis , 2000 .

[28]  Gustavo E. Scuseria,et al.  Linear Scaling Density Functional Calculations with Gaussian Orbitals , 1999 .

[29]  J. Kinoshita.  Simple Life Satisfies This Grad Student , 1996, Science.

[30]  Michael A Collins,et al.  Approximate ab initio energies by systematic molecular fragmentation. , 2005, The Journal of chemical physics.

[31]  M. Levitt,et al.  Theoretical studies of enzymic reactions: dielectric, electrostatic and steric stabilization of the carbonium ion in the reaction of lysozyme. , 1976, Journal of molecular biology.

[32]  Yixiang Cao,et al.  Correlated ab Initio Electronic Structure Calculations for Large Molecules , 1999 .

[33]  K. Morokuma,et al.  ONIOM: A Multilayered Integrated MO + MM Method for Geometry Optimizations and Single Point Energy Predictions. A Test for Diels−Alder Reactions and Pt(P(t-Bu)3)2 + H2 Oxidative Addition , 1996 .

[34]  Kohn,et al.  Density functional and density matrix method scaling linearly with the number of atoms. , 1996, Physical review letters.

[35]  John Z. H. Zhang,et al.  FULL AB INITIO COMPUTATION OF PROTEIN-WATER INTERACTION ENERGIES , 2004 .

[36]  Guohui Li,et al.  What is so special about Arg 55 in the catalysis of cyclophilin A? insights from hybrid QM/MM simulations. , 2003, Journal of the American Chemical Society.

[37]  Feliu Maseras,et al.  IMOMM: A new integrated ab initio + molecular mechanics geometry optimization scheme of equilibrium structures and transition states , 1995, J. Comput. Chem..

[38]  Darrin M. York,et al.  Quantum Mechanical Treatment of Biological Macromolecules in Solution Using Linear-Scaling Electronic Structure Methods , 1998 .