Molecular mechanism, and conformations

Gyorgy Keseru and Istvan Kolossvary, Molecular Mechanics and Conformational Analysis in Drug Design, Blackwell Science, Oxford, UK, 1999. 

Tel. 212-280-2577, e-mail sl model%cuchem.bitnet A user-friendly molecular modeling package for molecular mechanics and conformational searching of organic molecules, proteins, nucleic acids, and carbohydrates. AMBER-, MM2-, and MM3-like and OPLS force fields implicit solvation model. Reads Cambridge and Brookhaven PDB files. VAX, Convex, Alliant, Cray, and workstations. 

PC Model has some features that are not found in many other molecular mechanics programs. This is one of the few programs that outputs the energy given by the force field and the heat of formation and a strain energy. Atom types for describing transition structures in the MMX force field are included. There is a metal coordination option for setting up calculations with metal atoms. There are also molecular similarity and conformation search functions. 

McAllister, M. A., A. Perczel, P. Csaszar, and I. G. Csizmadia. 1993a. Peptide Models 5. Topological Features of Molecular Mechanics and Ab Initio 4D-Ramachandran Maps. Conformational Data for Ac-L-Ala-L-Ala-NHMe and For-L-Ala-L-Ala-NH2. J. Mol. Struct. (Theochem) 288,181-198. 

McAllister, M. A., Perczel, P. Csaszar, W. Viviani, J.-L. Rivail, and I. G. Csizmadia. 1993b. Peptide Models 4. Topological Features of Molecular Mechanics and Ab Initio 2D-Ramachandran Maps. Conformational Data for For-Gly-NH2, For-L-Ala-NH2, Ac-l-Ala-NHMe and For-L-Val-NH2. J. Mol. Struct. (Theochem) 288, 161-179. Mehrotra, P. K., M. Mezei, and D. L. Beveridge. 1984. Monte Carlo Determination of the Internal Energies of Hydration for the Ala Dipeptide in the C7, C5, aR, and Pn Conformations. Int. J. Quantum Chem. Quantum Biol. Symp. 11, 301-308. 

Schei, S. H. 1984a. 3-Chloro-l-Butene Gas-Phase Molecular Structure and Conformations as Determined by Electron Diffraction and by Molecular Mechanics and Ab Initio Calculations. J. Mol. Struct. 118, 319-332. 

Ingrid Pettersson and Tommy Liljefors, Molecular Mechanics Calculated Conformational Energies of Organic Molecules A Comparison of Force Fields. 

Molecular mechanics models differ both in the number and specific nature of the terms which they incorporate, as well as in the details of their parameterization. Taken together, functional form and parameterization, constitute what is termed a force field. Very simple force fields such as SYBYL, developed by Tripos, Inc., may easily be extended to diverse systems but would not be expected to yield quantitatively accurate results. On the other hand, a more complex force field such as MMFF94 (or more simply MMFF), developed at Merck Pharmaceuticals, while limited in scope to common organic systems and biopolymers, is better able to provide quantitative accounts of molecular geometry and conformation. Both SYBYL and MMFF are incorporated into Spartan. 

This chapter assesses the ability of molecular mechanics and quantum chemical models to properly assign preferred conformation, and to account quantitatively for differences in conformer energy as well as for barriers to rotation and inversion. The chapter ends with a discussion of ring inversion in cyclohexane. 

This chapter assesses the ability of both molecular mechanics and quantum chemical models to correctly assign the lowest-energy conformational arrangements in flexible molecules as well as aceount for energy differences between alternative conformers. It also assesses the performance of different models with regard to the calculation of barriers to single-bond rotation and pyramidal inversion. 

Investigations of the conformational properties of the flavan-3-ols and oligomeric proanthocyanidins have hitherto involved a variety of molecular mechanics and molecular orbital computations in combination with crystal structures, time-resolved fluorescence, as well as and NMR methods. Representative references to all these techniques may be found in the papers listed in Refs. 241-247, 250. These NMR papers incidentally also represent the major contributions regarding the conformation of proanthocyanidins, and may be summarized in a conformational context by reference to the significant contributions of Hatano and Hemingway. 

Myrtaceae), from which the related 2, 4, 6 -trihydroxy-3 -formyl-5 -methyldihydrochal-cone was also obtained. The NMR spectra of the synthetic formyl derivative show evidence for exchange broadening, which was attributed to conformational exchange between two stable hydrogen-bonded rotamers from molecular mechanics and ab initio calculations ... 

These approaches may include (1) purely empirical methods that try to simulate conformations by using classical molecular mechanics and adjustable parameters, still employed in very large molecular systems (2) potential energy determination with empirical and semiempirical functions consisting... 

To molecules of relatively large size, methods from molecular mechanics and force fields are also applied (84MI1 85JMC1301), and they have provided information on the conformational minima occurring in systems with several internal degrees of molecular mobility. 

A review of the Journal of Physical Chemistry A, volume 110, issues 6 and 7, reveals that computational chemistry plays a major or supporting role in the majority of papers. Computational tools include use of large Gaussian basis sets and density functional theory, molecular mechanics, and molecular dynamics. There were quantum chemistry studies of complex reaction schemes to create detailed reaction potential energy surfaces/maps, molecular mechanics and molecular dynamics studies of larger chemical systems, and conformational analysis studies. Spectroscopic methods included photoelectron spectroscopy, microwave spectroscopy circular dichroism, IR, UV-vis, EPR, ENDOR, and ENDOR induced EPR. The kinetics papers focused on elucidation of complex mechanisms and potential energy reaction coordinate surfaces. 

Pettersson, 1. and Liljefors, T. 1996. Molecular Mechanics Calculated Conformational Energies of Organic Molecules A Comparison of Force Fields , in Reviews in Computational Chemistry, Vol. 9, Lipkowitz, K. B. and Boyd, D. B., Eds., VCH New York, 167. 

---