Comparative analysis of the conformational profile of substance P using simulated annealing and molecular dynamics

Abstract

The present study describes an extensive conformational search of substance P using two different computational methods. On the one hand, the peptide was studied using the iterative simulated annealing, and on the other, molecular dynamics simulations at 300 and 400 K. With the former method, the peptide was studied in vacuo with a dielectric constant of 80, whereas using the latter study the peptide was studied in a box of TIP3P water molecules. Analysis of the results obtained using both methodologies was carried out using an in-house methodology using a cluster analysis method based on information theory. Comparison of the two sampling methodologies and the different environment used in the calculations is also analyzed. Finally, the conformational motifs that are characteristic of substance P in a hydrophilic environment are presented and compared with the experimental results available in the literature.

An Assessment of the Conformational Profile of Neuromedin B Using Different Computational Sampling Procedures

“…For this purpose, the CLASICO program (Corcho, 2004) was used to compute the pattern profile for every snapshot of MD and REMD trajectories, and is depicted in Figure 2a and Figure 2b, respectively. Accordingly, 105 439 (52.7%) patterns ( Figure 2a) were obtained for 200 000 snapshots of MD whereas 68 753 (68.7%) patterns ( Figure 2b) were identified for 100 000 snapshots of REMD trajectory.…”

“…Moreover, convergence seems to be attained in case of REMD after 100 ns as the appearance of new patterns was almost negligible at the end of trajectory. Secondary structure analysis was performed for every snapshot of MD and REMD calculations using the CLASICO program (Corcho, 2004) employing a three-residue window. Figures 3a-3b represents the statistics of the conformational motifs for each residue of the NMB peptide in MD and REMD trajectories, respectively.…”

“…The -turn motifs attained by residues of the NMB peptide were further classified into different types using two-residue window of the CLASICO program (Corcho, 2004), and are depicted in the Figures 4a-4b. The motifs obtained in MD trajectory (Figure 4a), shows the predominance of -turn type I between residues 4 and 9 with a high propensity of type II between residues 6 and 7.…”

“…The average distances corresponding to NMR NOE's were computed independently using the Clasterit algorithm of the CLASICO program (Corcho, 2004). Distances are reported as the average of the distance computed for each snapshot with a tolerance factor of ±1.96 standard deviations, covering a 95% of the variance assuming that they exhibit a normal distribution.…”

“…Inspection of Table 2 reveals that 89% of the structures are represented by the most abundant clusters. All the structures in each of the five most abundant clusters were analyzed to determine the conformational motifs attained by the NMB peptide, using CLASTERIT algorithm of the CLASICO program (Corcho, 2004).…”