Abstract
Although various higher-order protein structure prediction methods have been developed, almost all of them were developed based on the three-dimensional (3D) structure information of known proteins. Here we predicted the short protein structures by molecular dynamics (MD) simulations in which only Newton’s equations of motion were used and 3D structural information of known proteins was not required. To evaluate the ability of MD simulationto predict protein structures, we calculated seven short test protein (10–46 residues) in the denatured state and compared their predicted and experimental structures. The predicted structure for Trp-cage (20 residues) was close to the experimental structure by 200-ns MD simulation. For proteins shorter or longer than Trp-cage, root-mean square deviation values were larger than those for Trp-cage. However, secondary structures could be reproduced by MD simulations for proteins with 10–34 residues. Simulations by replica exchange MD were performed, but the results were similar to those from normal MD simulations. These results suggest that normal MD simulations can roughly predict short protein structures and 200-ns simulations are frequently sufficient for estimating the secondary structures of protein (approximately 20 residues). Structural prediction method using only fundamental physical laws are useful for investigating non-natural proteins, such as primitive proteins and artificial proteins for peptide-based drug delivery systems.
Highlights
Various methods for precise three-dimensional (3D) protein structure prediction have been developed [1,2,3]
The smallest root mean square deviation (RMSD) values during molecular dynamics (MD) trajectories compared with experimental structures are shown in Table 2 to evaluate whether short proteins can form
As depicted in this table, calculated structures that were close to the experimental structures (RMSD < 2.0 Å) were obtained for chignolin, CLN025, 2I9M and Trp-cage using 200-ns normal MD simulations at 300 K
Summary
Various methods for precise three-dimensional (3D) protein structure prediction have been developed [1,2,3]. In which 3D structural models are generated from known experimental homologue protein structures, can provide high precision structural models for drug discovery applications [4,5]. Even when the structure of a homolog is not available, structural modeling is possible using protein threading and ab initio protein modeling [2,6]. Refinement (I-TASSER) is one of the most successful protein structure prediction methods [7,8]. This method requires detection of structural templates from the Protein Data Bank (PDB) by threading.
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