The role of bonded terms in free energy simulations: 1. Theoretical analysis

被引:112
作者
Boresch, S
Karplus, M
机构
[1] Harvard Univ, Dept Chem, Cambridge, MA 02138 USA
[2] Univ Strasbourg, Inst Le Bel, Lab Chim Biophys, F-67000 Strasbourg, France
[3] Univ Vienna, Inst Theoret Chem, A-1090 Vienna, Austria
关键词
D O I
10.1021/jp981628n
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
The role of the bonded (bond stretching and bond angle) force-field terms in free energy simulations is examined. It is shown that the proper treatment of such terms depends on the choice of the free energy methodology (single or dual topology). Furthermore, while there are no problems in describing changes in bonded terms, care has to be used in creating or destroying them in a molecular dynamics simulation. An approach that avoids the singularity caused by a bond with a zero force constant is outlined. Changes in bond stretching or bond angle terms are shown to give rise to vibrational, Jacobian factor, and potential-of-mean-force-type (pmf) contributions. The meaning of bond stretching and bond angle bending free energy components obtained in single and dual topology simulations and their connection to these three contributions is investigated. Due to the different end states used in single and dual topology simulations, the pmf contribution is projected on different free energy components. In certain dual topology methods, vibrational and Jacobian factor contributions are not included in the free energy difference. Therefore, single free energy differences (e.g., the free energy difference between two molecules in the gas phase and in solution) often cannot be compared directly between single and dual topology methods. However, identical double free energy differences (e.g., free energy differences of solvation) are obtained in all cases. The present analysis emphasizes the importance of the details of the simulation methodology in interpreting the results for bonded terms and reconciles apparently contradictory findings in the literature.
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页码:103 / 118
页数:16
相关论文
共 75 条
  • [11] BORESCH S, 1988, J PHYS CHEM A, V103, P119
  • [12] DECOMPOSITION OF INTERACTION FREE-ENERGIES IN PROTEINS AND OTHER COMPLEX-SYSTEMS
    BRADY, GP
    SHARP, KA
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1995, 254 (01) : 77 - 85
  • [13] CHARMM - A PROGRAM FOR MACROMOLECULAR ENERGY, MINIMIZATION, AND DYNAMICS CALCULATIONS
    BROOKS, BR
    BRUCCOLERI, RE
    OLAFSON, BD
    STATES, DJ
    SWAMINATHAN, S
    KARPLUS, M
    [J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 1983, 4 (02) : 187 - 217
  • [14] BROOKS CL, 1988, ADV CHEM PHYSICS, V71
  • [15] A 2ND GENERATION FORCE-FIELD FOR THE SIMULATION OF PROTEINS, NUCLEIC-ACIDS, AND ORGANIC-MOLECULES
    CORNELL, WD
    CIEPLAK, P
    BAYLY, CI
    GOULD, IR
    MERZ, KM
    FERGUSON, DM
    SPELLMEYER, DC
    FOX, T
    CALDWELL, JW
    KOLLMAN, PA
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (19) : 5179 - 5197
  • [16] CROSS AJ, 1986, CHEM PHYS LETT, V128, P198, DOI 10.1016/0009-2614(86)80325-6
  • [17] FREE-ENERGY CALCULATIONS ON PROTEIN STABILITY - THR-157-] VAL-157 MUTATION OF T4 LYSOZYME
    DANG, LX
    MERZ, KM
    KOLLMAN, PA
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1989, 111 (22) : 8505 - 8508
  • [18] STATISTICAL-MECHANICS OF SOLVENT-INDUCED FORCES AND VIBRATIONAL FREQUENCY-SHIFTS - LOW-DENSITY EXPANSIONS AND MONTE-CARLO SIMULATIONS
    DESOUZA, LES
    GUERIN, CBE
    BENAMOTZ, D
    SZLEIFER, I
    [J]. JOURNAL OF CHEMICAL PHYSICS, 1993, 99 (12) : 9954 - 9961
  • [19] Additivity principles in biochemistry
    Dill, KA
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (02) : 701 - 704
  • [20] RELATIVE HYDRATION FREE-ENERGIES OF NUCLEIC-ACID BASES
    ELCOCK, AH
    RICHARDS, WG
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (17) : 7930 - 7931