Biomolekulare Modellierung: Ziele, Probleme, Perspektiven

Abstract

Computerverfahren auf der Grundlage von Molekülmodellen gewinnen in Biologie, biologischer Chemie und Biophysik zunehmend an Bedeutung. Da nur wenige Eigenschaften biomolekularer Systeme durch Messungen zugänglich sind, können Computersimulationen experimentelle Daten ergänzen, indem sie nicht nur Durchschnittswerte, sondern auch Verteilungen und Zeitreihen jeder bestimmbaren Größe liefern, z. B. Konformationsverteilungen oder Wechselwirkungen zwischen Teilen eines Systems. Die Anwendung moderner biomolekularer Modellierungsverfahren wird zurzeit durch vier grundlegende Probleme eingeschränkt: 1) das Kraftfeldproblem, 2) das Suchproblem, 3) das Ensembleproblem und 4) das Experimentalproblem. Diese vier Probleme werden anhand praktischer Beispiele erläutert, außerdem werden Lösungsperspektiven aufgezeigt.

Biomolecular Modeling: Goals, Problems, Perspectives

“…In the case of peptides possessing 20 rotatable torsional angles in their backbone, the use of physical, realistic force fields representing the particular (nonbonding) interactions between the various residues results in a reduction from 10 9 possible conformers to 10 3 relevant conformers. [144][145][146] This is illustrated in Figure 11, where the number of conformations visited during a MD simulation of a polypeptide and of another polymer of equal length are shown. This number grows sublinearly for the b-heptapeptide in methanol and levels off at about 200 conformations (Figure 11 A), whereas the number of visited (relevant) conformations for a poly(hydroxybutanoate) molecule of similar length in chloroform grows linearly with time (Figure 11 B), as would be expected considering the number of possible conformations for either molecule is about 10 9 .…”

“…A surprising result after the simulation of many polypeptides: The number of unfolded conformations visited in MD simulations of (un)folding equilibria of a host of polypeptides and peptoids is much smaller than theoretically possible. [144][145][146] Biomolecular Modeling…”

A Combined Solid‐State NMR and MD Characterization of the Stability and Dynamics of the HET‐s(218‐289) Prion in its Amyloid Conformation

“…[12] Similar observations have been made for amyloids formed by Tau, [13] a-Synuclein, [14] and the Y145Stop variant of the human prion protein. [15] Recent advances in hardware and methodology [16] have allowed for molecular dynamics (MD) simulations of small fibrils consisting of several monomer units on the nanosecond timescale. [17][18][19][20][21] Herein, we have performed simulations of a HET-s-A C H T U N G T R E N N U N G (218-289) trimer in explicit solvent within a classical model (GROMOS force field parameter set 45A3).…”

The Role of the Conformational Dynamics of Glutathione S-Transferase Epsilon Class on Insecticide Resistance inAnopheles gambiae

“…1,17 MD simulations provide an atomic description of the time-evolution of conformations of a system due to its singular property of probing space and time scales simultaneously. [20][21][22] For this The Role of the Conformational Dynamics of Glutathione S-Transferase Epsilon Class J. Braz. Chem.…”

“…1,17 MD simulations provide an atomic description of the time-evolution of conformations of a system due to its singular property of probing space and time scales simultaneously. [20][21][22] For this reason, it is a powerful technique to explore conformational transitions of biomolecules at the atomic level. We report on the structural rearrangements of the DDT pocket cap, which led to the partial occlusion of the G-site, and displacement of the Glu116 (Glu120 in GSTE5) towards the thiol group of GSH upon GSH binding.…”