R. K. Mishra

Molecular orbital studies on the conformation of phospholipids. II. Preferred conformations of hydrocarbon chains and molecular organization in biomembranes

Abstract The preferred conformations of the nonpolar β and γ (hydrocarbon) chains in phospholipids have been derived using EHT and CNDO calculations. These calculations indicate that the possible conformations of phospholipids are highly restricted. The calculations find support from X-ray diffraction studies and NMR measurements on model compounds. When considering conformations relevant to structures in cell membranes, a further selection is possible because of the fact that in aqueous solutions hydrophobic interactions stabilize an arrangement where the hydrocarbon chains (β and γ) are stacked almost parallel to one another, leading to a bilayer structure. The various models for β and γ-chains which satisfy this condition have been compared and it has been shown that of these only four are favoured by energy considerations. These arrangements differ from one another in the orientation of the β-chain and γ-chains in the interior of the bilayer structure. A low energy pathway connects these conformations and thus the molecule can easily flip from one stable bilayer arrangement to another. The possible conformations of the polar group (α) are likewise restricted. The proposed model provides explanations to a number of dynamic and static properties of phospholipids, in particular to the observed NMR coupling constants, 1 H and 13 C relaxation times, studies based on ESR spin labels and the observed X-ray diffraction results on model compounds.

Calculation of the minimum energy conformation of biomolecules using a global optimization technique I. Methodology and application to a model molecular fragment (Normal pentane)

Abstract The conformational energy of a molecule is minimized with respect to interatomic distances using Bremermanns method of unconstrained global optimization (1970). The optimal set of distances is then used for calculating the preferred conformation of the molecule. A simultaneous optimization of all the dihedral angles is achieved. The classical potential function is used in this study. An illustration of the method is given by applying it to normal pentane, which is a commonly occurring fragment of biomolecules. Results show that, for the standard geometry (bond lengths and bond angles), the all-trans) conformation is the preferred one. However, fluctuations of the geometry within the limits of the vibrational spectra can lead to preferred conformations that are not necessarily all-trans.

Calculation of the minimum energy conformation of biomolecules using a global optimization technique II. Conformation of N-acetylglycine N-methyl amide, a model dipeptide unit

Abstract Further to our study of molecular fragments, the preferred conformation of N -acetylglycine N -methyl amide is calculated by the global optimization method proposed earlier (Subba Rao, Tyagi & Mishra,1981). The classical potential function is used in this study. The results obtained agree with the classical energy calculations of other workers. This study also provides a further test of the efficacy of the method.

Calculation of the minimum energy conformation of biomolecules using a global optimization technique. III. Conformation of acetylcholine using molecular fragments

Abstract The preferred conformation of acetylcholine as a function of six variable dihedral angles is arrived at by calculating the conformation of its fragments and then putting the fragments together in an overlapping manner. The conformation of the complete molecule is also calculated by varying all the six dihedral angles simultaneously. The classical potential function is used in the calculations. The results of the two approaches agree very well with each other, with the classical energy calculations of other workers and with crystallographic data. These results demonstrate both the efficacy of our method (Subba Rao, Tyagi & Mishra, 1981a) and the validity of the “fragment approach” to conformational calculations.

A study of the intermolecular association in living systems. IV. Studies on a model molecular fragment (pentane)

Abstract The low-lying energy states for the association of two molecules of n -pentane are determined by keeping one molecule fixed and rotating the second molecule simultaneously about its own x-, y -, and z- axes and also around the first molecule, all rotations being carried out from 0° to 360° in steps of 20° The interaction energy is calculated at each step, the form of the interaction energy used is the one given by Claverie & Rein (1969). Results show that only a very limited number of orientations lead to energy states that are within 5 kcal mol −1 of the minimum energy state.