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P S Stern

Publications and source records attributed to P S Stern.

7 recordsLinked to original sources
PubMed1994

Comparison of systematic search and database methods for constructing segments of protein structure.

Two principal methods of determining the conformation of short pieces of polypeptide backbone in proteins have been developed: using a database of known structures and systematically generating all conformations. In this paper, we compare the effectiveness of these two techniques. The completeness of the database for segments of different lengths is examined and it is found to contain most conformations for segments seven residues long, but to deteriorate rapidly for longer regions. When the database segment is to be incorporated into the rest of a structure, at least seven residues are required to build four new residues, because of the need to position the segment relative to the rest of the structure. It is found that such positioning using flanking residues results in large errors in the inserted region. We conclude that the database method is currently not effective for comparative modeling, even for short segments. The systematic search procedure is found to generate almost all structures of short segments found in proteins. In contrast to the database method, low root mean square error structures are obtained for a set of trial segments embedded in the rest of a protein structure. Thus, it should be considered the method of choice.

Computer Simulation↗
PubMed1991

Predicting antigenic sites on proteins.

The ability to predict antigenic sites on proteins is of major importance for the production of synthetic peptide vaccines and synthetic peptide probes of antibody structure. Many predictive methods, based on various assumptions about the nature of the antigenic response have been proposed and tested. This review will discuss the principles underlying the various approaches to predicting antigenic sites and will attempt to answer the question of how well they work.

Amino Acid Sequence↗
PubMed1985

Protein normal-mode dynamics: trypsin inhibitor, crambin, ribonuclease and lysozyme.

We have developed a new method for modelling protein dynamics using normal-mode analysis in internal co-ordinates. This method, normal-mode dynamics, is particularly well suited for modelling collective motion, makes possible direct visualization of biologically interesting modes, and is complementary to the more time-consuming simulation of molecular dynamics trajectories. The essential assumption and limitation of normal-mode analysis is that the molecular potential energy varies quadratically. Our study starts with energy minimization of the X-ray co-ordinates with respect to the single-bond torsion angles. The main technical task is the calculation of second derivative matrices of kinetic and potential energy with respect to the torsion angle co-ordinates. These enter into a generalized eigenvalue problem, and the final eigenvalues and eigenvectors provide a complete description of the motion in the basic 0.1 to 10 picosecond range. Thermodynamic averages of amplitudes, fluctuations and correlations can be calculated efficiently using analytical formulae. The general method presented here is applied to four proteins, trypsin inhibitor, crambin, ribonuclease and lysozyme. When the resulting atomic motion is visualized by computer graphics, it is clear that the motion of each protein is collective with all atoms participating in each mode. The slow modes, with frequencies of below 10 cm-1 (a period of 3 ps), are the most interesting in that the motion in these modes is segmental. The root-mean-square atomic fluctuations, which are dominated by a few slow modes, agree well with experimental temperature factors (B values). The normal-mode dynamics of these four proteins have many features in common, although in the larger molecules, lysozyme and ribonuclease, there is low frequency domain motion about the active site.

Aprotinin↗