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Equilibrium configurations of rigid building blocks with multiple embedded interaction sites are investigated, as a coarse-grained approach for conformational sampling of protein structures with known secondary structure. First, hypothetical structures of asymmetric shapes, and pairs of rods composed of multiple interaction sites are considered. The rods are either disconnected or joined by a flexible loop. The sites are assumed to interact with a classical 6-12 Lennard-Jones potential. Subsequently, the investigation is extended to the study of two disconnected α helices composed of homogeneous interaction sites and to the ROP monomer, a small protein consisting of two heterogeneous α helices connected by a loop. Residue-specific long-range and short-range potentials extracted from a protein database are used. A Monte Carlo procedure combined with an energy minimization algorithm, originally developed by Li and Scheraga [Proc. Natl. Acad. Sci. USA 84, 6611 (1987)] is used to generate a set of low energy conformations over the full conformational space. Results show that: (i) The potential of mean force between two rods as a whole exhibits an inverse linear dependence on the separation between rods despite the individual sites interacting via a 6-12 Lennard-Jones potential. (ii) As the length of the rods (or helices) increases, they tend to align parallel to one other. (iii) This tendency to become parallel is enhanced when the density of interaction sites is higher. (iv) The angle between the principal axes of the rods is found to scale as n-5/3 with the number n of sites. (v) The native conformation of the ROP monomer, including the detailed rotational states of the virtual bonds located in the loop connecting the α helices is correctly predicted. This lends support to the adoption of such a coarse-grained model and its parameters for future simulations. © 1997 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Whether knowledge-based intra-molecular inter-residue potentials are valid to represent inter-molecular interactions taking place at protein-protein interfaces has been questioned in several studies. Differences in the chain connectivity effect and in residue packing geometry between interfaces and single chain monomers have been pointed out as possible sources of distinct energetics for the two cases. In the present study, the interfacial regions of protein-protein complexes are examined to extract inter-molecular inter-residue potentials, using the same statistical methods as those previously adopted for intra-molecular residue pairs. Two sets of energy parameters are derived, corresponding to solvent-mediation and 'average residue' mediation. The former set is shown to be highly correlated (correlation coefficient 0.89) with that previously obtained for inter-residue interactions within single chain monomers, while the latter exhibits a weaker correlation (0.69) with its intra-molecular counterpart. In addition to the close similarity of intra- and inter-molecular solvent-mediated potentials, they are shown to be significantly more residue-specific and thereby discriminative compared to the residue-mediated ones, indicating that solvent-mediation plays a major role in controlling the effective inter-residue interactions, either at interfaces, or within single monomers. Based on this observation, a reduced set of energy parameters comprising 20 one-body and 3 two-body terms is proposed (as opposed to the 20 × 20 tables of inter-residue potentials), which reproduces the conventional 20 × 20 tables with a correlation coefficient of 0.99. [ABSTRACT FROM AUTHOR]

A simple model of sphere packing has been investigated as an ideal model for long-range interactions for the packing of non-bonded residues in protein structures. By superposing all residues, the geometry of packing around a central residue is investigated. It is found that all residues conform almost perfectly to this lattice model for sphere packing when a radius of 6.5 Å is used to define non-bonded (virtual) interacting residues. Side-chain positions with respect to sequential backbone segments are relatively regular as well. This lattice can readily be used in conformation simulations to reduce the conformational space. [ABSTRACT FROM AUTHOR]