Author
William L. Jorgensen
Other affiliations: University of California, Los Angeles, University of Barcelona, McDaniel College ...read more
Bio: William L. Jorgensen is an academic researcher from Yale University. The author has contributed to research in topics: Racism & Monte Carlo method. The author has an hindex of 108, co-authored 586 publications receiving 95112 citations. Previous affiliations of William L. Jorgensen include University of California, Los Angeles & University of Barcelona.
Papers published on a yearly basis
Papers
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TL;DR: In this article, the authors compared the Bernal Fowler (BF), SPC, ST2, TIPS2, TIP3P, and TIP4P potential functions for liquid water in the NPT ensemble at 25°C and 1 atm.
Abstract: Classical Monte Carlo simulations have been carried out for liquid water in the NPT ensemble at 25 °C and 1 atm using six of the simpler intermolecular potential functions for the water dimer: Bernal–Fowler (BF), SPC, ST2, TIPS2, TIP3P, and TIP4P. Comparisons are made with experimental thermodynamic and structural data including the recent neutron diffraction results of Thiessen and Narten. The computed densities and potential energies are in reasonable accord with experiment except for the original BF model, which yields an 18% overestimate of the density and poor structural results. The TIPS2 and TIP4P potentials yield oxygen–oxygen partial structure functions in good agreement with the neutron diffraction results. The accord with the experimental OH and HH partial structure functions is poorer; however, the computed results for these functions are similar for all the potential functions. Consequently, the discrepancy may be due to the correction terms needed in processing the neutron data or to an effect uniformly neglected in the computations. Comparisons are also made for self‐diffusion coefficients obtained from molecular dynamics simulations. Overall, the SPC, ST2, TIPS2, and TIP4P models give reasonable structural and thermodynamic descriptions of liquid water and they should be useful in simulations of aqueous solutions. The simplicity of the SPC, TIPS2, and TIP4P functions is also attractive from a computational standpoint.
33,683 citations
TL;DR: In this article, the parametrization and testing of the OPLS all-atom force field for organic molecules and peptides are described, and the parameters for both torsional and non-bonded energy properties have been derived, while the bond stretching and angle bending parameters have been adopted mostly from the AMBER force field.
Abstract: The parametrization and testing of the OPLS all-atom force field for organic molecules and peptides are described. Parameters for both torsional and nonbonded energetics have been derived, while the bond stretching and angle bending parameters have been adopted mostly from the AMBER all-atom force field. The torsional parameters were determined by fitting to rotational energy profiles obtained from ab initio molecular orbital calculations at the RHF/6-31G*//RHF/6-31G* level for more than 50 organic molecules and ions. The quality of the fits was high with average errors for conformational energies of less than 0.2 kcal/mol. The force-field results for molecular structures are also demonstrated to closely match the ab initio predictions. The nonbonded parameters were developed in conjunction with Monte Carlo statistical mechanics simulations by computing thermodynamic and structural properties for 34 pure organic liquids including alkanes, alkenes, alcohols, ethers, acetals, thiols, sulfides, disulfides, a...
12,024 citations
TL;DR: A complete set of intermolecular potential functions has been developed for use in computer simulations of proteins in their native environment and they have been parametrized directly to reproduce experimental thermodynamic and structural data on fluids.
Abstract: A complete set of intermolecular potential functions has been developed for use in computer simulations of proteins in their native environment. Parameters are reported for 25 peptide residues as well as the common neutral and charged terminal groups. The potential functions have the simple Coulomb plus Lennard-Jones form and are compatible with the widely used models for water, TIP4P, TIP3P, and SPC. The parameters were obtained and tested primarily in conjunction with Monte Carlo statistical mechanics simulations of 36 pure organic liquids and numerous aqueous solutions of organic ions representative of subunits in the side chains and backbones of proteins. Bond stretch, angle bend, and torsional terms have been adopted from the AMBER united-atom force field. As reported here, further testing has involved studies of conformational energy surfaces and optimizations of the crystal structures for four cyclic hexapeptides and a cyclic pentapeptide. The average root-mean-square deviation from the X-ray structures of the crystals is only 0.17 A for the atomic positions and 3% for the unit cell volumes. A more critical test was then provided by performing energy minimizations for the complete crystal of the protein crambin, including 182 water molecules that were initially placed via a Monte Carlo simulation. The resultant root-mean-square deviation for the non-hydrogen atoms is still ca. 0.2 A and the variation in the errors for charged, polar, and nonpolar residues is small. Improvement is apparent over the AMBER united-atom force field which has previously been demonstrated to be superior to many alternatives. Computer simulations are undoubtedly destined to became an increasingly important means for investigating the structures and dynamics of biomolecular systems.' At the heart of such theoretical calculations are the force fields that describe the interatomic interactions and the mechanics of deformations of the molecules.* There is also little doubt that there will be a continual evolution in force fields with added complexity and improved performance paralleling the availability of computer resources. Our own efforts in this area over the last few years have resulted in the OPLS potential functions for proteins whose development and performance are summarized here. These potential functions have a simple form and they have been parametrized directly to reproduce experimental thermodynamic and structural data on fluids. Consequently, they are computationally efficient and their description of proteins in solution or crystalline environments should be superior to many alterantives that have been developed with limited condensed-phase data. The latter point is pursued here primarily through calculations on the crystal structures for four cyclic hexapeptides, a cyclic pentapeptide, and the protein crambin. Improvements are apparent in comparison to the AMBER united-atom force field3 which has previously been shown to be superior to many alternative^.^ (1) Beveridge, D. L., Jorgensen, W. L., Eds. Ann. N.Y. Acad. Sci. 1986, 482. ( 2 ) For reviews, see: (a) Levitt, M. Annu. Reu. Biophys. Eioeng. 1982, 11, 251. (b) McCammon, J. A. Rep. Prog. Phys. 1984, 47, 1. (3) Weiner, S. J.; Kollman, P. A.; Case, D. A,; Singh, U. C.; Ghio, C.; Alagona, G.; Profeta, S.; Weiner, P. J. Am. Chem. SOC. 1984, 106, 765. Parametrization The peptide residues of proteins contain readily identifiable organic subunits such as amides, hydrocarbons, alcohols, thioethers, etc. In view of this and since data are available on the corresponding pure organic liquids, our approach to developing a force field for proteins was to build it up from parameters demonstrated to yield good descriptions of organic liquids. U1timately, the force field would need to treat both intramolecular terms for bond stretches, angle bends, and torsions, as well as the intermolecular and intramolecular nonbonded interactions. The latter are generally accepted to be the most difficult part of the problem and have been our focus.3 A simple, computationally efficient form was chosen to represent the nonbonded interactions through Coulomb and Lennard-Jones terms interacting between sites centered on nuclei (eq 1). Thus, the intermolecular inter-
4,328 citations
TL;DR: In this article, a fitting technique combines using accurate ab initio data as the target, choosing an efficient fitting subspace of the whole potential energy surface, and determining weights for each of the fitting points based on magnitudes of the potential energy gradient.
Abstract: We present results of improving the OPLS-AA force field for peptides by means of refitting the key Fourier torsional coefficients. The fitting technique combines using accurate ab initio data as the target, choosing an efficient fitting subspace of the whole potential-energy surface, and determining weights for each of the fitting points based on magnitudes of the potential-energy gradient. The average energy RMS deviation from the LMP2/cc-pVTZ(-f)//HF/6-31G** data is reduced by ca. 40% from 0.81 to 0.47 kcal/mol as a result of the fitting for the electrostatically uncharged dipeptides. Transferability of the parameters is demonstrated by using the same alanine dipeptide-fitted backbone torsional parameters for all of the other dipeptides (with the appropriate side-chain refitting) and the alanine tetrapeptide. Parameters of nonbonded interactions have also been refitted for the sulfur-containing dipeptides (cysteine and methionine), and the validity of the new Coulombic charges and the van der Waals σ's ...
3,516 citations
TL;DR: Together, the improvements made to both the small molecule and protein force field lead to a high level of accuracy in predicting protein-ligand binding measured over a wide range of targets and ligands (less than 1 kcal/mol RMS error) representing a 30% improvement over earlier variants of the OPLS force field.
Abstract: The parametrization and validation of the OPLS3 force field for small molecules and proteins are reported. Enhancements with respect to the previous version (OPLS2.1) include the addition of off-atom charge sites to represent halogen bonding and aryl nitrogen lone pairs as well as a complete refit of peptide dihedral parameters to better model the native structure of proteins. To adequately cover medicinal chemical space, OPLS3 employs over an order of magnitude more reference data and associated parameter types relative to other commonly used small molecule force fields (e.g., MMFF and OPLS_2005). As a consequence, OPLS3 achieves a high level of accuracy across performance benchmarks that assess small molecule conformational propensities and solvation. The newly fitted peptide dihedrals lead to significant improvements in the representation of secondary structure elements in simulated peptides and native structure stability over a number of proteins. Together, the improvements made to both the small mole...
2,127 citations
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TL;DR: In this article, the authors compared the Bernal Fowler (BF), SPC, ST2, TIPS2, TIP3P, and TIP4P potential functions for liquid water in the NPT ensemble at 25°C and 1 atm.
Abstract: Classical Monte Carlo simulations have been carried out for liquid water in the NPT ensemble at 25 °C and 1 atm using six of the simpler intermolecular potential functions for the water dimer: Bernal–Fowler (BF), SPC, ST2, TIPS2, TIP3P, and TIP4P. Comparisons are made with experimental thermodynamic and structural data including the recent neutron diffraction results of Thiessen and Narten. The computed densities and potential energies are in reasonable accord with experiment except for the original BF model, which yields an 18% overestimate of the density and poor structural results. The TIPS2 and TIP4P potentials yield oxygen–oxygen partial structure functions in good agreement with the neutron diffraction results. The accord with the experimental OH and HH partial structure functions is poorer; however, the computed results for these functions are similar for all the potential functions. Consequently, the discrepancy may be due to the correction terms needed in processing the neutron data or to an effect uniformly neglected in the computations. Comparisons are also made for self‐diffusion coefficients obtained from molecular dynamics simulations. Overall, the SPC, ST2, TIPS2, and TIP4P models give reasonable structural and thermodynamic descriptions of liquid water and they should be useful in simulations of aqueous solutions. The simplicity of the SPC, TIPS2, and TIP4P functions is also attractive from a computational standpoint.
33,683 citations
28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: It is demonstrated that arbitrary accuracy can be achieved, independent of system size N, at a cost that scales as N log(N), which is comparable to that of a simple truncation method of 10 A or less.
Abstract: The previously developed particle mesh Ewald method is reformulated in terms of efficient B‐spline interpolation of the structure factors This reformulation allows a natural extension of the method to potentials of the form 1/rp with p≥1 Furthermore, efficient calculation of the virial tensor follows Use of B‐splines in place of Lagrange interpolation leads to analytic gradients as well as a significant improvement in the accuracy We demonstrate that arbitrary accuracy can be achieved, independent of system size N, at a cost that scales as N log(N) For biomolecular systems with many thousands of atoms this method permits the use of Ewald summation at a computational cost comparable to that of a simple truncation method of 10 A or less
17,897 citations
TL;DR: The CHARMM (Chemistry at Harvard Macromolecular Mechanics) as discussed by the authors is a computer program that uses empirical energy functions to model macromolescular systems, and it can read or model build structures, energy minimize them by first- or second-derivative techniques, perform a normal mode or molecular dynamics simulation, and analyze the structural, equilibrium, and dynamic properties determined in these calculations.
Abstract: CHARMM (Chemistry at HARvard Macromolecular Mechanics) is a highly flexible computer program which uses empirical energy functions to model macromolecular systems. The program can read or model build structures, energy minimize them by first- or second-derivative techniques, perform a normal mode or molecular dynamics simulation, and analyze the structural, equilibrium, and dynamic properties determined in these calculations. The operations that CHARMM can perform are described, and some implementation details are given. A set of parameters for the empirical energy function and a sample run are included.
14,725 citations
TL;DR: A new implementation of the molecular simulation toolkit GROMACS is presented which now both achieves extremely high performance on single processors from algorithmic optimizations and hand-coded routines and simultaneously scales very well on parallel machines.
Abstract: Molecular simulation is an extremely useful, but computationally very expensive tool for studies of chemical and biomolecular systems Here, we present a new implementation of our molecular simulation toolkit GROMACS which now both achieves extremely high performance on single processors from algorithmic optimizations and hand-coded routines and simultaneously scales very well on parallel machines The code encompasses a minimal-communication domain decomposition algorithm, full dynamic load balancing, a state-of-the-art parallel constraint solver, and efficient virtual site algorithms that allow removal of hydrogen atom degrees of freedom to enable integration time steps up to 5 fs for atomistic simulations also in parallel To improve the scaling properties of the common particle mesh Ewald electrostatics algorithms, we have in addition used a Multiple-Program, Multiple-Data approach, with separate node domains responsible for direct and reciprocal space interactions Not only does this combination of a
14,032 citations