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1.
Jan Fuhrmann Alexander Rurainski Hans‐Peter Lenhof Dirk Neumann 《Journal of computational chemistry》2010,31(9):1911-1918
We present a Lamarckian genetic algorithm (LGA) variant for flexible ligand‐receptor docking which allows to handle a large number of degrees of freedom. Our hybrid method combines a multi‐deme LGA with a recently published gradient‐based method for local optimization of molecular complexes. We compared the performance of our new hybrid method to two non gradient‐based search heuristics on the Astex diverse set for flexible ligand‐receptor docking. Our results show that the novel approach is clearly superior to other LGAs employing a stochastic optimization method. The new algorithm features a shorter run time and gives substantially better results, especially with increasing complexity of the ligands. Thus, it may be used to dock ligands with many rotatable bonds with high efficiency. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010 相似文献
2.
J. Papadakis G. S. Fanourgakis S. C. Farantos M. Founargiotakis 《Journal of computational chemistry》1997,18(8):1011-1022
The most robust numerical algorithms for unconstrained optimization that involve a line search are tested in the problem of locating stable structures and transition states of atomic microclusters. Specifically, the popular quenching technique is compared with conjugate gradient and variable metric algorithms in the Mg+Arn clusters. It is found that the variable metric method BFGS combined with an approximate line minimization routine is the most efficient, and it shows global convergence properties. This technique is applied to find a few hundred stationary points of Mg+Ar12 and to locate isomerization paths between the two most stable icosahedral structures found for Mg+Ar12. The latter correspond to a solvated and a nonsolvated ion, respectively. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 :1011–1022, 1997 相似文献
3.
Jan Fuhrmann Alexander Rurainski Hans‐Peter Lenhof Dirk Neumann 《Journal of computational chemistry》2009,30(9):1371-1378
We present a novel method for the local optimization of molecular complexes. This new approach is especially suited for usage in molecular docking. In molecular modeling, molecules are often described employing a compact representation to reduce the number of degrees of freedom. This compact representation is realized by fixing bond lengths and angles while permitting changes in translation, orientation, and selected dihedral angles. Gradient‐based energy minimization of molecular complexes using this representation suffers from well‐known singularities arising during the optimization process. We suggest an approach new in the field of structure optimization that allows to employ gradient‐based optimization algorithms for such a compact representation. We propose to use exponential mapping to define the molecular orientation which facilitates calculating the orientational gradient. To avoid singularities of this parametrization, the local minimization algorithm is modified to change efficiently the orientational parameters while preserving the molecular orientation, i.e. we perform well‐defined jumps on the objective function. Our approach is applicable to continuous, but not necessarily differentiable objective functions. We evaluated our new method by optimizing several ligands with an increasing number of internal degrees of freedom in the presence of large receptors. In comparison to the method of Solis and Wets in the challenging case of a non‐differentiable scoring function, our proposed method leads to substantially improved results in all test cases, i.e. we obtain better scores in fewer steps for all complexes. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009 相似文献
4.
L. B. Morales R. Garduo&#x;Jurez J. M. Aguilar&#x;Alvarado F. J. Riveros&#x;Castro 《Journal of computational chemistry》2000,21(2):147-156
We have developed and implemented a tabu search heuristic (TS) to determine the best energy minimum for oligopeptides. Our test molecule was Met‐enkephalin, a pentapetide that over the years has been used as a validation model for many global optimizers. The test potential energy function was ECEPP/3. Our tabu search implementation is based on assigning integer values to the variables to be optimized, and in facilitating the diversification and intensification of the search. The final output from the TS is treated with a local optimizer, and our best result competes both in quality and CPU time with those reported in the literature. The results indicate that TS is an efficient algorithm for conformational searches. We present a parallel TS version along with experimental results that show that this algorithm allows significant increases in speed. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 147–156, 2000 相似文献
5.
采用以熵最小算法为基本原理的化学计量学方法,结合气相色谱-质谱联用分析法,对玫瑰精油及茉莉花挥发油中的2对同分异构体重叠峰进行重建分析,并分别得到各组分的重建质谱,同时采用NIST数据库相似度检索、质谱碎片信息比对及程序升温指数对分析得到的各组分进行定性分析。通过分析,分别从玫瑰精油和茉莉花挥发油的GC-MS重叠峰中分离得到1对同分异构体。分析结果显示,采用熵最小算法可以成功地对重叠峰中的各组分进行定性分析。该研究为类似同分异构体混合物中各组分的测定提供了参考。 相似文献
6.
Paramfit: Automated optimization of force field parameters for molecular dynamics simulations 
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下载免费PDF全文 The generation of bond, angle, and torsion parameters for classical molecular dynamics force fields typically requires fitting parameters such that classical properties such as energies and gradients match precalculated quantum data for structures that scan the value of interest. We present a program, Paramfit, distributed as part of the AmberTools software package that automates and extends this fitting process, allowing for simplified parameter generation for applications ranging from single molecules to entire force fields. Paramfit implements a novel combination of a genetic and simplex algorithm to find the optimal set of parameters that replicate either quantum energy or force data. The program allows for the derivation of multiple parameters simultaneously using significantly fewer quantum calculations than previous methods, and can also fit parameters across multiple molecules with applications to force field development. Paramfit has been applied successfully to systems with a sparse number of structures, and has already proven crucial in the development of the Assisted Model Building with Energy Refinement Lipid14 force field. © 2014 Wiley Periodicals, Inc. 相似文献
7.
D. Byrne J. Li E. Platt B. Robson P. Weiner 《Journal of computer-aided molecular design》1994,8(1):67-82
Summary The modelling of biological molecules by molecular dynamics is beset by a range of problems. The most important of these is the multiple-minima problem. The deep metastable minima can cause difficulties in proper equilibration of a molecular system and result in the simulated system being trapped in a long-lived metastable state. One way to overcome these problems is to re-engineer the Newtonian Rules in order to more efficiently search conformational space. Re-engineering of the Newtonian Rules implies a redesign of the physical laws arising from them. This is done in various ways by the RUSH, Hybrid Monte Carlo and PEACS algorithms. This paper explores applications of these algorithms, and compares them to a traditional molecular dynamics method. 相似文献
8.
遗传算法是一种模仿自然进化进程的新颖的启发式优化方法。通过它，人们可以在计算机上对所需的各种问题实施进化操作，最终产生理想的结果。遗传算法现已被广泛于计算机辅助设计、工程设计、系统模拟等领域并取得了极大的成功。本文拟对遗传算法在对大、中、小分子的构象搜寻中的应用作一较全面的综述。 相似文献
9.
We have developed a new docking program that explores ligand flexibility. This program can be applied to database searches. The program is similar in concept to earlier efforts, but it has been automated and improved. The algorithm begins by selecting an anchor fragment of a ligand. This fragment is protonated, as needed, and then placed in the receptor by the DOCK algorithm, followed by minimization using a simplex method. Finally, the conformations of the remaining parts of the putative ligands are searched by a limited backtrack method and minimized to get the most stable conformation. To test the efficiency of this method, the program was used to regenerate ten ligand–protein complex structures. In all cases, the docked ligands basically reproduced the crystallographic binding modes. The efficiency of this method was further tested by a database search. Ten percent of molecules from the Available Chemicals Directory (ACD) were docked to a dihydrofolate reductase structure. Most of the top-ranking molecules (7 of the top 13 hits) are dihydrofolate or methotrexate derivatives, which are known to be DHFR inhibitors, demonstrating the suitability of this program for screening molecular databases. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1812–1825, 1997 相似文献
10.
We present a series of conformational search calculations on the aggregation of short peptide fragments that form fibrils similar to those seen in many protein mis-folding diseases. The proteins were represented by a face-centered cubic lattice model with the conformational energies calculated using the Miyazawa-Jernigan potential. The searches were performed using algorithms based on the Metropolis Monte Carlo method, including simulated annealing and replica exchange. We also present the results of searches using the tabu search method, an algorithm that has been used for many optimization problems, but has rarely been used in protein conformational searches. The replica exchange algorithm consistently found more stable structures then the other algorithms, and was particularly effective for the octamers and larger systems. 相似文献
11.
The identification of RNA secondary structure has been an important tool for the characterization of nucleic acids. Computational structure prediction has been an effective approach toward this end, but improvement of established methods is often slow and reliant on redundant methodology. Here we present a novel consensus scoring approach, created to incorporate inputs from an array of established methods with the goal of producing outputs that contain mutual structures from these programs. This method is implemented in RNAdemocracy, a python program capable of competing with existing methods. This ensemble approach was limited by commonalities in established methods like parameter sourcing, which may lead to agreement error, an unavoidable outcome due to the limit of available RNA structure datasets. The modular construction of RNAdemocracy allows for its easy upgrading and customization to suit user’s needs. RNAdemocracy, while capable of accurate predictions, is best suited to guide users to regions of the sequence space that exhibit agreement instead of a totally reliant predictor of structure. It is also capable of grading predictions for potential accuracy by providing a percentage of consensus between contributing methods in the final structure. 相似文献
12.
Christoph Grebner Johannes Becker Svetlana Stepanenko Bernd Engels 《Journal of computational chemistry》2011,32(10):2245-2253
Efficient conformational search or sampling approaches play an integral role in molecular modeling, leading to a strong demand for even faster and more reliable conformer search algorithms. This article compares the efficiency of a molecular dynamics method, a simulated annealing method, and the basin hopping (BH) approach (which are widely used in this field) with a previously suggested tabu‐search‐based approach called gradient only tabu search (GOTS). The study emphasizes the success of the GOTS procedure and, more importantly, shows that an approach which combines BH and GOTS outperforms the single methods in efficiency and speed. We also show that ring structures built by a hydrogen bond are useful as starting points for conformational search investigations of peptides and organic ligands with biological activities, especially in structures that contain multiple rings. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011 相似文献
13.
Fatih Yaar Tarik elik Bernd A. Berg Hagai Meirovitch 《Journal of computational chemistry》2000,21(14):1251-1261
The multicanonical (Muca) Monte Carlo method enables simulating a system over a wide range of temperatures and thus has become an efficient tool for studying spin glasses, first‐order phase transitions, the helix–coil transition of polypeptides, and protein folding. However, implementation of the method requires calculating the multicanonical weights by an iterative procedure that is not straightforward and is a stumbling block for newcomers. A recursive procedure that takes into account the statistical errors of all previous iterations and thus enables an automatic calculation of the weights without the need for human intervention after each iteration has been proposed. This procedure, which has already been tested successfully for lattice systems, is extended here to continuum models of peptides and proteins. The method is examined in detail and tested for models of the pentapeptide Leu‐enkephalin (Tyr‐Gly‐Gly‐Phe‐Leu) described by the potential energy function ECEPP. Because of the great interest in the structural mapping of the low‐energy region of biomolecules, the energy of structures selected from the Muca trajectory is minimized. The extent of conformational coverage provided by the method is examined and found to be very satisfactory. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 1251–1261, 2000 相似文献
14.
The energy‐based refinement of protein structures generated by fold prediction algorithms to atomic‐level accuracy remains a major challenge in structural biology. Energy‐based refinement is mainly dependent on two components: (1) sufficiently accurate force fields, and (2) efficient conformational space search algorithms. Focusing on the latter, we developed a high‐resolution refinement algorithm called GRID. It takes a three‐dimensional protein structure as input and, using an all‐atom force field, attempts to improve the energy of the structure by systematically perturbing backbone dihedrals and side‐chain rotamer conformations. We compare GRID to Backrub, a stochastic algorithm that has been shown to predict a significant fraction of the conformational changes that occur with point mutations. We applied GRID and Backrub to 10 high‐resolution (≤ 2.8 Å) crystal structures from the Protein Data Bank and measured the energy improvements obtained and the computation times required to achieve them. GRID resulted in energy improvements that were significantly better than those attained by Backrub while expending about the same amount of computational resources. GRID resulted in relaxed structures that had slightly higher backbone RMSDs compared to Backrub relative to the starting crystal structures. The average RMSD was 0.25 ± 0.02 Å for GRID versus 0.14 ± 0.04 Å for Backrub. These relatively minor deviations indicate that both algorithms generate structures that retain their original topologies, as expected given the nature of the algorithms. © 2012 Wiley Periodicals, Inc. 相似文献
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16.
A modified genetic algorithm approach has been applied to atomic Ar clusters and molecular water clusters up to (H2O)13. Several genetic operators are discussed which are suitable for real-valued space-fixed atomic coordinates and Euler angles. The performance of these operators has been systematically investigated. For atomic systems, it is found that a mix of operators containing a coordinate-averaging operator is optimal. For angular coordinates, the situation is less clear. It appears that inversion and two-point crossover operators are the best choice. © 1997 John Wiley & Sons, Inc. J Comput Chem 18: 1233–1244 相似文献
17.
David J. Diller Christophe L. M. J. Verlinde 《Journal of computational chemistry》1999,20(16):1740-1751
Several global optimization algorithms were applied to the problem of molecular docking: random walk and Metropolis Monte Carlo Simulated Annealing as references, and Stochastic Approximation with Smoothing (SAS), and Terminal Repeller Unconstrained Subenergy Tunneling (TRUST) as new methodologies. Of particular interest is whether any of these algorithms could be used to dock a database of typical small molecules in a reasonable amount of time. To address this question, each algorithm was used to dock four small molecules presenting a wide range of sizes, degrees of flexibility, and types of interactions. Of the algorithms tested, only stochastic approximation with smoothing appeared to be sufficiently fast and reliable to be useful for database searches. This algorithm can reliably dock relatively small and fairly rigid molecules in a few seconds, and larger and more flexible molecules in a few minutes. The remaining algorithms tested were able to reliably dock the small and fairly rigid molecules, but showed little or no reliability when docking large or flexible molecules. In addition, to decrease the error in the typical grid-based energy evaluations a new form of interpolation, logarithmic interpolation, is proposed. This interpolation scheme is shown to both quantitatively reduce the numerical error and practically to improve the docking results. © 1999 John Wiley & Sons, Inc. J Comput Chem 20: 1740–1751, 1999 相似文献
18.
SKATE is a docking prototype that decouples systematic sampling from scoring. This novel approach removes any interdependence between sampling and scoring functions to achieve better sampling and, thus, improves docking accuracy. SKATE systematically samples a ligand's conformational, rotational and translational degrees of freedom, as constrained by a receptor pocket, to find sterically allowed poses. Efficient systematic sampling is achieved by pruning the combinatorial tree using aggregate assembly, discriminant analysis, adaptive sampling, radial sampling, and clustering. Because systematic sampling is decoupled from scoring, the poses generated by SKATE can be ranked by any published, or in‐house, scoring function. To test the performance of SKATE, ligands from the Asetex/CDCC set, the Surflex set, and the Vertex set, a total of 266 complexes, were redocked to their respective receptors. The results show that SKATE was able to sample poses within 2 Å RMSD of the native structure for 98, 95, and 98% of the cases in the Astex/CDCC, Surflex, and Vertex sets, respectively. Cross‐docking accuracy of SKATE was also assessed by docking 10 ligands to thymidine kinase and 73 ligands to cyclin‐dependent kinase. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010 相似文献
19.
Genetic algorithms based on wavelet transform for resolving simulated overlapped spectra 总被引：2，自引：0，他引：2
Wavelet transform-based genetic algorithms are proposed for resolving simulated overlapped spectra. Wavelet transform as a derivative method is used for de-noising, for deducting background absorption as well as for peak finding in order to get an estimation of parameters of unresolved spectra. Then genetic algorithms, using the estimations of parameters as input values, are employed to resolve unresolved bands. As a consequence, a good optimized solution was achieved since the reliable estimation of initial values can greatly facilitate the convergence of genetic algorithms and the calculation time is shortened accordingly. 相似文献
20.
A new methodology for the prediction of molecular crystal structures using only the atomic connectivity of the molecule under consideration is presented. The approach is based on the global minimization of the lattice enthalpy of the crystal. The modeling of the electrostatic interactions is accomplished through a set of distributed charges that are optimally and automatically selected and positioned based on results of quantum mechanical calculations. A four-step global optimization algorithm is used for the identification of the local minima of the lattice enthalpy surface. A parallelized implementation of the algorithm permits a much more extensive search of the solution space than has hitherto been possible, allowing the identification of crystal structures in less frequently occurring space groups and with more than one molecule in the asymmetric unit. The algorithm has been applied successfully to the prediction of the crystal structures of 3-aza-bicyclo(3.3.1)nonane-2,4-dione (P2(1)/a, Z' = 1), allopurinol (P2(1)/c, Z' = 1), 1,3,4,6,7,9-hexa-azacycl(3.3.3)azine (Pbca, Z' = 2), and triethylenediamine (P6(3)/m, Z' = 1). In all cases, the experimentally known structure is among the most stable predicted structures, but not necessarily the global minimum. 相似文献