Random Coil to Globular Thermal Response (H3.1) Figure 3. Residue map (neighboring residues along the contour within the range of interaction) of protein at different temperatures (T = 0.0160–0.0260) with BT potential. doi:10.1371/journal.pone.0049352.g003 figure 6). The estimate of the effective spatial dimension (De < 1/n) of the protein with the MJ potential leads to De<2, a random coil (ideal chain) at the high temperature T = 0.025, and De<3, a solid globular structure (n = 1/3) at the low temperature T = 0.013. Similar scaling fits are also consistent with the results of BT and BFKV potentials (figure 7). Note that at high temperatures, thermal energy dominates over residue-residue interaction. Therefore, the protein chain behaves like an ideal polymer chain (with excluded volume constraints) as it should. Discussion and Conclusions A coarse-grained Monte Carlo simulation is used to investigate the effect of temperature on the conformation of a protein, histone H3.1, using three knowledge-based potentials, the classical MJ, BT and BFKV. The protein is described by a coarse-grained chain of residues (nodes) tethered together by fluctuating covalent bonds. Each residue interacts with other residues within a range of interaction using a generalized LJ potential where knowledge- based contact matrices (MJ, BT, BFKV) are used as an input for the residue-residue interaction. The coarse-grained interaction matrix thus captures the specificity of each residue. Extensive simulations are performed for a range of temperatures for sufficiently long time steps to identify changes in conformation and stability. We have examined a number of local and global physical quantities including the energy of each residue, its mobility, mean square displacement of the center of the mass of the protein, radius of gyration and its structure factor. Thermal responses resulting from the three potentials are compared and similarities and differences are pointed out. Global conformation (measured by the radius of gyration and the structure factor) resulting from the collective dynamics of residues in histone H3.1 depends on temperature. How it changes depends on the interaction potential and the range of temperature. One of the general characteristics common to results from all three potentials (MJ, BT, BFKV) is that the protein undergoes a systematic conformational transformation: globular conformation at low temperature to a random coil at high temperatures (simple but unique to H3.1). The range over which such a systematic response occurs, however, depends on the potential matrix. For example, DTMJ < 0.013–0.020 with the MJ potential, and shifts towards higher temperatures DTBT < 0.018–0.026 with the BT potential and lower temperatures DTBFKV < 0.006–0.013 with the BFKV potential. The magnitudes of Rg converge to a steady-state value with a random coil structure with all potentials in the high temperature regime. Variation of Rg with the temperature shows an anomaly with the BFKV potential where the magnitude of Rg decreases on raising the temperature in a range DTA < 0.015– 0.018 before reaching its saturation. Despite the improved potentials suggested by both groups, Betancourt and Thirumalai [7] and Bastolla et al. [8], it is not clear which potential is better than the other over the entire range of temperatures. Results from both potentials, BT and BFKV, show opposite shift with respect to the MJ potential. One of the main problems is the lack of explicit experimental data on the variation of the Rg of the histone H3.1 with temperature. PLOS ONE | www.plosone.org 5 November 2012 | Volume 7 | Issue 11 | e49352