Computational simulations of the conformational behaviour of the adhesive proteins RGDS fragment.

Many adhesive proteins present in extracellular matrices and in blood contain the tetrapeptide sequence -Arg-Gly-Asp-Ser- (or RGDS) at their cell recognition site. Since this sequence, or similar ones, was found in many proteins involved in major biological mechanisms, conformational investigations were performed on the RGDS fragment. A preliminary review of available crystal structures indicates that the RxDy sequences exhibit 3 well-defined structural patterns: one corresponding to a strong interaction between the Arg and Asp ionic side chains which are only about 4 A apart, one with the ions separated by about 8 A, and another in which the side chains are further apart (about 11 A). The conformational behaviour of the isolated RGDS fragment was next tackled using sequential building, Monte Carlo and molecular dynamics computational techniques. Analysis of the RGDS sequence conformational possibilities, as simulated in vacuum and in water solution, indicates that they can be classified into several conformational classes, which correspond roughly to the behaviour of the RGDS fragment as observed in protein matrices. This suggests the possibility of understanding the biological role of the RGDS or parent sequences in recognition processes.

Computer simulation of the conformational behavior of cholecystokinin fragments: conformational families of sulfated CCK8.

Display methods, such as principal component analysis, and clustering methods were applied to a sample of cholecystokinin, (sulfated CCK8) conformations obtained from a Monte Carlo simulation. It is shown that six families of conformations can entirely describe the sample. Each family represents a typical conformer. These theoretical models are in agreement with recent experimental results which stress the predominance of folded conformers in aqueous medium.

Theoretical conformational analysis of phospholipids. I. Study of the interactions between phospholipid molecules by use of semi-empirical methods with the explicit introduction of polar headgroup interactions.

We present a theoretical conformational analysis of a system composed of seven dipalmitoylphosphatidylethanolamine molecules in interaction. The combined use of classical semi-empirical methods for the polar headgroup region with mechanical statistical calculations for the aliphatic chains permits the evaluation of the free energy for a phospholipids molecule. The free energy variation in function of the mean intermolecular interchain distance gives information about the main lipid bilayer phase transition. It appears, however, necessary to take into account the hydration of the polar headgroups.

Theoretical conformational analysis of phospholipids. II. Role of hydration in the gel to liquid crystal transition of phospholipids.

To obtain a satisfactory agreement between computed transition temperatures and those determined experimentally, we introduce explicitly water molecules which hydrate the polar headgroup of dipalmitoylphosphatidylethanolamine molecules. The calculated free energy curves as a function of the intermolecular interchain distance and the degree of hydration of the polar groups permit the determination of the transition of the phospholipid system from the gel to the liquid crystalline phase. The detailed structure of the hydration shell is defined using the supermolecular approach.