Molecular mechanics (MM4) study of amines

The MM4 force field has been extended to include aliphatic amines. About 20 amines have been examined to obtain a set of useful molecular mechanics parameters for this class. The vibrational spectra of seven amines (172 frequencies) calculated by MM4 have an overall rms error of 27 cm(-1), compared with corresponding MM4 value of 24 cm(-1) for alkanes. The rms and signed average errors of the moments of inertia of nine simple amines compared with the experimental data were 0.18% and -0.004%, respectively. The heats of formation of 30 amines were also studied. The MM4 weighted standard deviation is 0.41 kcal/mol, compared with experiment. Electronegativity effects occur in the hydrocarbon portion of an amine from the nitrogen, and are accounted for by including electronegativity induced changes in bond lengths and angles, and induced dipole-dipole interactions in the molecule. Negative hyperconjugation results from the presence of the lone pair of electrons on nitrogen, and leads to the Bohlmann bands in the infrared, and also to strong and unusual geometric changes in the molecules (Bohlmann effect), all of which are fairly well accounted for. The conformational energies in amines appear to be less straightforward than those for most other classes of molecules, apparently because of the Bohlmann effect, and these are probably not yet completely understood. In general, the agreement between the MM4 calculated results and the available data is reasonably good.     

Molecular mechanics (MM3) calculations on lithium amide compounds

The MM3 force field has been extended to deal with the lithium amide molecules that are widely used as efficient catalysts for stereoselective asymmetric synthesis. The MM3 force field parameters have been determined on the basis of the ab initio MP2/6-31G* and/or DFT (B3LYP/6-31G*, B3-PW91/6-31G*) geometry optimization calculations. To evaluate the electronic interactions specific to the lithium amides derived from the diamine molecules properly, the Lewis bonding potential term for the interaction between the lithium atom and the nonbonded adjacent electronegative atom such as nitrogen was introduced into the MM3 force field. The bond dipoles were evaluated correctly from the electronic charges on the atoms calculated by fitting to the electrostatic potential at points selected. The MM3 results on the molecular structures, conformational energies, and vibrational spectra show good agreement with those from the quantum mechanical calculations.     

Ab initio calculations and molecular mechanics (MM3) force field development for ammonium and protonated aliphatic amines

The geometries and vibrational frequencies of 11 training molecules containing the ammonium ion moiety were calculated at the MP2/6-31+G* level of theory. Various torsional energy profiles were also calculated using this basis set. From those ab initio calculations, a molecular mechanics (MM3) force field was developed using our Parameter Analysis and Refinement Toolkit System (PARTS). Using this set of parameters, the MM3 force field was found to well reproduce the molecular geometries and vibrational spectra for the all training molecules. CPU time was reduced from days to seconds. The availability of this new force field dramatically increases the feasibility of the computer-assisted drug design involving ammonium and protonated amino groups. © 1997 by John Wiley & Sons, Inc. J Comput Chem 18 : 1371–1391, 1997     

Molecular mechanics (MM4) calculations on carbonyl compounds part I: aldehydes

Aliphatic aldehydes have been studied with the aid of the MM4 force field. The structures, moments of inertia, vibrational spectra, conformational energies, barriers to internal rotation, and dipole moments have been examined for six compounds (nine conformations). MM4 parameters have been developed to fit the indicated quantities to the wide variety of experimental data. Ab initio (MP2) and density functional theory (B3LYP) calculations have been used to augment and/or replace experimental data, as appropriate. Because more, and to some extent, better, data have become available since MM3 was developed, it was anticipated that the overall accuracy of the information calculated with MM4 would be better than with MM3. The best single measure of the overall accuracy of a force field is the accuracy to which the moments of inertia of a set of compounds (from microwave spectroscopy) can be reproduced. For all of the 20 moments (seven conformations) experimentally known for the aldehyde compounds, the MM4 rms error is 0.30%, while with MM3, the most accurate force field presently available, the rms error over the same set is 1.01%. The calculation of the vibrational spectra was also improved overall. For the four aldehydes that were fully analyzed (over a total of 78 frequencies), the rms errors with MM4 and MM3 are 18 and 38 cm^?1, respectively. These improvements came from several sources, but the major ones were separate parameters involving the carbonyl carbon for formaldehyde, the alkyl aldehydes and the ketones, and new crossterms featured in the MM4 force field that are not present in the MM3 version. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1396–1425, 2001     

Efficient treatment of out-of-plane bend and improper torsion interactions in MM2, MM3, and MM4 molecular mechanics calculations

Simple and very efficient formulas are presented for four-body out-of-plane bend (used in MM2 and MM3 force fields) and improper torsion (used in the MM4 force field) internal coordinates and their first and second derivatives. The use of a small set of bend and stretch intermediates allows for order of magnitude decreases in calculation time for potential energies and their first and second derivatives, which are required in molecular mechanics calculations. The formulas are eminently suitable for use in molecular simulations of systems with complicated bond networks. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1804–1811, 1997     

Molecular mechanics studies (MM4) of sulfides and mercaptans

The MM4 force field has been extended to the title class of compounds. The vibrational spectra, structures, conformational equilibria, and heats of formation have been studied for 47 conformers of 29 compounds. In general, the properties may be calculated with accuracy that is competitive with that for hydrocarbons. The structures are better fit than previously because of the inclusion of a torsion–bend interaction term, which has its origin in the lone pair (Bohlmann) effect. Available experimental data do not suffice to yield detailed torsional potentials, or geometries as a function of torsion angle, and these quantities were determined by ab initio calculations at the MP2/6-31G* level. The rms error in the calculated frequencies of seven representative structures (with a total of 64 experimental and 96 ab initio frequencies) is 25 cm⁻¹. The heats of formation for 23 compounds have a weighted rms error of 0.36 kcal/mol. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1827–1847, 1997     

Molecular mechanics (MM3) parameterization of hydroxylamine and methyl derivatives

Based on results of electron diffraction, gas phase infrared spectroscopy (IR), and MP2/6-31 + G* ab initio calculations, a set of molecular mechanics (MM3) parameters was developed for molecules containing the N(sp³)—O(sp³) moiety. Using this set of parameters, MM3 is able to reproduce structures (bond lengths and bond angles) and vibrational spectra satisfactorily. © 1994 by John Wiley & Sons, Inc.     

MM3(96) parameterization for camptothecin analogs: An ab initio and molecular mechanics study

Torsional parameters for MM3(96) were derived for the missing atom types present in thenatural product camptothecin (CPT). Potential energy curves were calculated via ab initiocalculations on representative compounds for dihedral angles containing these missingparameters. Gaussian 92 at the restricted Hartree–Fock level of theory using thestandard 6-31G** and 4-31G** basis sets, was used for all the quantum-mechanicscalculations. Missing MM3 torsional terms were obtained by optimizing the V1, V2 and V3parameters such that MM3 could reproduce the ab initio torsional profile. MM3 calculatedmolecular structures that compare well with the ab initio results. Using the newly developedparameters, conformational analyses and QSAR studies of camptothecin analogs wereundertaken. MM3 predicts two distinct boatlike conformations for the -hydroxy lactonemoiety. The low-energy lactone conformation predicted by MM3 is in general agreement withreported X-ray crystal structures of CPT iodoacetate and 7-ethyl-10-(4-piperidino)piperidinylcarbonyloxy CPT HCl as well as the ab initio structure of a CPT-like-hydroxy lactone.     

Improving the Q2MM method for transition state force field modeling

The Quantum‐to‐molecular mechanics method (Q2MM) for converting quantum mechanical transition states (TSs) to molecular mechanical minima has been modified to allow a fit to the “natural” reaction mode eigenvalue. The resulting force field gives an improved representation of the energy curvature at the TS, but can potentially give false responses to steric interactions. Ways to address this problem while staying close to the “natural” TS force field are discussed. © 2014 Wiley Periodicals, Inc.     

Ab initio parametrized MM3 force field for the metal-organic framework MOF-5

A new valence force field has been developed and validated for a particular class of coordination polymers known as nanoporous metal-organic frameworks (MOFs), introduced recently by the group of Yaghi. The experimental, structural, and spectroscopic data in combination with density functional theory calculations on several model systems were used to parametrize the bonded terms of the force field, which explicitly treats the metal-oxygen interactions as partially covalent as well as distinguishes different types of oxygens in the framework. Both the experimental crystal structure of MOF-5 and vibrational infrared spectrum are reproduced reasonably well. The proposed force field is believed to be useful in atomistic simulations of adsorption/diffusion of guest molecules inside the flexible pores of this important class of MOF materials.     

Molecular mechanics conformational analysis of tylosin

The conformations of the 16-membered macrolide antibiotic tylosin were studied with molecular mechanics (AMBER* force field) including modelling of the effect of the solvent on the conformational preferences (GB/SA). A Monte Carlo conformational search procedure was used for finding the most probable low-energy conformations. The present study provides complementary data to recently reported analysis of the conformations of tylosin based on NMR techniques. A search for the low-energy conformations of protynolide, a 16-membered lactone containing the same aglycone as tylosin, was also carried out, and the results were compared with the observed conformation in the crystal as well as with the most probable conformations of the macrocyclic ring of tylosin. The dependence of the results on force field was also studied by utilizing the MM3 force field. Some particular conformations were computed with the semiempirical molecular orbital methods AM1 and PM3.     

Molecular mechanics models for tetracycline analogs

Tetracyclines (Tcs) are an important family of antibiotics that bind to the ribosome and several proteins. To model Tc interactions with protein and RNA, we have developed a molecular mechanics force field for 12 tetracyclines, consistent with the CHARMM force field. We considered each Tc variant in its zwitterionic tautomer, with and without a bound Mg(2+). We used structures from the Cambridge Crystallographic Data Base to identify the conformations likely to be present in solution and in biomolecular complexes. A conformational search by simulated annealing was undertaken, using the MM3 force field, for tetracycline, anhydrotetracycline, doxycycline, and tigecycline. Resulting, low-energy structures were optimized with an ab initio method. We found that Tc and its analogs all adopt an extended conformation in the zwitterionic tautomer and a twisted one in the neutral tautomer, and the zwitterionic-extended state is the most stable in solution. Intermolecular force field parameters were derived from a standard supermolecule approach: we considered the ab initio energies and geometries of a water molecule interacting with each Tc analog at several different positions. The final, rms deviation between the ab initio and force field energies, averaged over all forms, was 0.35 kcal/mol. Intramolecular parameters were adopted from either the standard CHARMM force field, the ab initio structure, or the earlier, plain Tc force field. The model reproduces the ab initio geometry and flexibility of each Tc. As tests, we describe MD and free energy simulations of a solvated complex between three Tcs and the Tet repressor protein.     

Molecular mechanics (MM2) calculations and cone angles of phosphine ligands

Molecular mechanics (MM2) calculations were performed on 54 conformations of 18 phosphines (PH₃; PH_3−nR_n, where n = 1,…3, and R = Me and Et, n = 1 or 2 and R =ⁱPr, and n = 1 and R =^tBu, PMe₂Et, PMeEt₂, and PPhMe₂, and PPh₂R where R = Me, Et, ⁱPr, ^tBu and Ph). The results are compared to those previously obtained from MINDO/3 and MNDO calculations, and to experimental data. Single conformer cone angles and weighted average cone angles were calculated from MM2 optimized geometries employing Tolman's general definition, and they are compared to Tolman's values, MINDO/3 results, and T.L. Brown's E_R values. Of the cone angle definitions used, the weighted average values are suggested as the best single representation of phosphine ligand sizes. The steric parameters (cone angle and E_R values) alone, and in conjunction with electronic parameters, are correlated with experimental data.     

Comparative performance of MM3(92) and two TINKER MM3 versions for the modeling of carbohydrates

The 1992 version of MM3 was largely used for modeling mono-, di-, and trisaccharides. In later versions of MM3 improvements were made in some parameters that may be important for carbohydrates. This corrected MM3 force field is part of the Tinker package, freely available (as its 4.1 version), and included in the Chem 3D Ultra 8.0 package (as the 3.7 version). The latter version lacks the corrections to the standard bond lengths produced by electronegativity and anomeric effects, whereas the Tinker 4.1 version only lacks the latter correction. The present work compares the performance of the three MM3 versions (and in some cases, DFT and/or HF/ab initio procedures) on several carbohydrate model problems as the chair and rotamer equilibria in 2-hydroxy- and 2-methoxytetrahydropyran, hydrogen bonding in cis-2,3-dihydroxytetrahydropyran, and the potential energy surfaces around the glycosidic bonds of two sulfated disaccharides and two trisaccharides. Tinker MM3 can be used accurately to estimate carbohydrate energies and geometries, and-with the help of some programming-to pursue studies on the potential energy surfaces of di- and trisaccharides. In most cases results obtained using the three MM3 versions are similar, although large energy differences are obtained when comparing a rotameric distribution around a O-C-O-H dihedral, which is almost forced to the exo-anomeric position by the Tinker versions. In other systems smaller energy differences are found, but they can nevertheless lead to a different global minimum when comparing conformers of similar energy. MM3(92) establishes better the differences between the bond lengths in both anomers, as an expected expression of the anomeric correction.     

在微机上实现分子力学模拟B-DNA

DNA是典型的螺旋结构，关于它的模拟方法有很多种，本文将探讨一种能在微机上用分子力学模拟B型DNA的方法，该方法以Cs Chem3D软件包中MM2为支持力场，搭建和几何优化B－DNA，并对模拟B－DNA的构象特征进行详细分析以证实此方法的可行性。     

Molecular mechanics calculations (MM3) on sulfones

The structures of several sulfones, including dimethyl sulfone, methyl ethyl sulfone, methyl vinyl sulfone, and diphenyl sulfone, have been fit with the MM3 force field to existing experimental data from electron diffraction and microwave spectroscopy. The vibrational spectra have also been fit for six of these compounds. The torsional parameters for the aliphatic sulfones were fit to ab initio 6-31G data. Heats of formation were also fit. © 1993 John Wiley & Sons, Inc.     

Molecular mechanics force field parameterization of the fluorescent probe rhodamine 6G using automated frequency matching

Novel single-molecule fluorescence experimental techniques have prompted a growing need to develop refined computational models of dye-tagged biomolecules. As a necessary first step towards useful molecular simulations of fluorescence-labeled biomolecules, we have derived a force field for the commonly used dye, rhodamine 6G (R6G). A novel automated method is used that includes fitting the molecular mechanics potential to both vibrational frequencies and eigenvector projections derived from quantum chemical calculations. The method is benchmarked on a series of aromatic molecules then applied to derive new parameters for R6G. The force field derived reproduces well the crystal structure of R6G.     

Molecular mechanics calculations on carbonyl compounds. III. Cycloketones

Molecular mechanics (MM4) calculations were carried out on cycloketones for ring sizes ranging from 4 to 11 carbon atoms. The MM4 relative energies for the various conformations of the cycloketones were compared to density functional theory (DFT) calculations (B3LYP/6‐31G*), which were also carried out in this work. For small ring sizes (n=4–6), calculated molecular geometries, dipole moments, moments of inertia, and vibrational spectra were compared to experimental data. The axial–equatorial energy differences in methyl‐substituted cyclohexanones were also calculated by MM4 and compared to ab initio, DFT, and experimental results. The results of the MM4 studies on cycloketones showed significant improvement from those of MM3 calculations performed in parallel with the MM4 calculations. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1451–1475, 2001     

Partial hessian fitting for determining force constant parameters in molecular mechanics

We present a new protocol for deriving force constant parameters that are used in molecular mechanics (MM) force fields to describe the bond‐stretching, angle‐bending, and dihedral terms. A 3 × 3 partial matrix is chosen from the MM Hessian matrix in Cartesian coordinates according to a simple rule and made as close as possible to the corresponding partial Hessian matrix computed using quantum mechanics (QM). This partial Hessian fitting (PHF) is done analytically and thus rapidly in a least‐squares sense, yielding force constant parameters as the output. We herein apply this approach to derive force constant parameters for the AMBER‐type energy expression. Test calculations on several different molecules show good performance of the PHF parameter sets in terms of how well they can reproduce QM‐calculated frequencies. When soft bonds are involved in the target molecule as in the case of secondary building units of metal‐organic frameworks, the MM‐optimized geometry sometimes deviates significantly from the QM‐optimized one. We show that this problem is rectified effectively by use of a simple procedure called Katachi that modifies the equilibrium bond distances and angles in bond‐stretching and angle‐bending terms. © 2016 Wiley Periodicals, Inc.     

A molecular mechanics (MM3) study of fluorinated hydrocarbons

A molecular mechanics study of small saturated hydrocarbons (up to C-6), substituted by up to six fluorines was carried out with the MM3 force field. Perfluorobutane and Teflon were also studied. A parameter set was developed for use in the calculation of bond lengths, bond angles, torsion angles, conformational energies, barriers to rotation, dipole moments, moments of inertia and vibrational frequencies for these compounds. The results are in good agreement with experiment when only one or two fluorines are present, but some rather large discrepancies were noted when the F/H ratio becomes high. These can be taken into account only by using a force field more complicated than MM3. Some of the requirements of such a force field are delineated. Some pertinent ab initio results are also reported in this article.