<div>Dear All,</div><div>I'm running set of umbrella sampling simulations to get the PMF of a disaccharide binding to a protein.</div><div>I followed the tutorial provided by Justin and changed the values of necessary parameters according to my system.</div>
<div>The mdp file for umbrella sampling simulations is as follows:</div><div>-------------------------------------------</div><div>; Pull code<br>pull = umbrella<br>pull_geometry = distance ; can't get PMF with direction<br>
pull_dim = N N Y<br>pull_start = yes<br>pull_ngroups = 1<br>pull_group0 = active_site<br>pull_pbcatom0 = 575<br>pull_group1 = new<br>pull_pbcatom1 = 1500<br>pull_init1 = 0<br>
pull_rate1 = 0.0<br>pull_k1 = 750 ; kJ mol^-1 nm^-2<br>pull_nstxout = 1000 ; every 2 ps<br>pull_nstfout = 1000 ; every 2 ps</div><div>----------------------------------------------------</div>
<div> </div><div>Active site in the pull_group0 being the residues in the binding site and new in the pull_group1 being the disaccharide.</div><div>Initially I did an SMD run where I separated the disaccharide from the binding upto 1.5nm in distance.</div>
<div> </div><div>When I started running the umbrella sampling simulations, I used the conformations with approximately 0.1nm difference starting from an initial separation of 0.3nm between the binding site residues and disaccharide.</div>
<div>My question is: when I run g_wham and get the profile, the pmf reaches a plateau, but its not completely horizontal. It drops down a little. Is it acceptable to have the pmf reach a plateau but not completely horizontal?</div>
<div>In the histogram, the first two windows have good overlap and are narrow distributions where as the later windows are spread out.</div><div>I have tried to decrease the distance from 0.1 nm to 0.05 nm and still the sampling around 0.5-0.75 of Xi region does not sample well. </div>
<div>Is there anything that you could suggest?</div><div> </div><div>I have uploaded the plots of profile and histograms.</div><div> </div><div>PMF Plot link: <a href="http://img801.imageshack.us/i/pmf.png/">http://img801.imageshack.us/i/pmf.png/</a></div>
<div>Histogram link: <a href="http://img217.imageshack.us/i/histoy.png/">http://img217.imageshack.us/i/histoy.png/</a></div><div> </div><div><br>Thanks for your time</div><div> </div><div>Sai Ramadugu</div>