BcompB meeting July 16th

BcompB meeting on simulations methods for allosteric signal propagation

Tuesday July 16th, 2-3pm, C42

Our next BcompB meeting will take place on July 16th, 2-3pm in C42. We will hear about and discuss simulation methods to look into allosteric communication/signal propagation.

Eric Lang and Sofia Oliveira will be speaking about methods that they have developed and applied.

All welcome!

Eric Lang
Calculated pKa Variations Expose Dynamic Allosteric Communication Networks

Allosteric regulation of protein function, the process by which binding of an effector molecule provokes a functional response from a distal site, is critical for metabolic pathways. Yet, the way the allosteric signal is communicated remains elusive, especially in dynamic, entropically driven regulation mechanisms for which no major conformational changes are observed. To identify these dynamic allosteric communication networks, we have developed an approach that monitors the pKa variations of ionizable residues over the course of molecular dynamics simulations performed in the presence and absence of an allosteric regulator. As the pKa of ionizable residues depends on their environment, it represents a simple metric to monitor changes in several complex factors induced by binding an allosteric effector. These factors include Coulombic interactions, hydrogen bonding, and solvation, as well as backbone motions and side chain fluctuations. The predictions that can be made with this method concerning the roles of ionizable residues for allosteric communication can then be easily tested experimentally by changing the working pH of the protein or performing single point mutations.


Sofia Oliveira

Signal propagation in nicotinic receptors: contributions from equilibrium and nonequilibrium simulations

Nicotinic acetylcholine receptors (nAChRs) modulate synaptic transmission in the nervous system. These receptors have emerged as therapeutic targets in drug discovery for treating several conditions, including Alzheimer’s, pain and nicotine addiction. Despite the impressive progress made in the study of this family of receptors, the conformational changes induced by agonist binding/unbinding and how those are communicated to the ion channel remain poorly defined. This is fundamentally important for understanding biological function as well as crucial for rational drug discovery. Here, we have developed a novel computational strategy combing extensive equilibrium and nonequilibrium molecular dynamics simulations to map dynamic and structural changes induced by nicotine in the human α4β2 nAChR. This approach revealed a striking pattern of communication between the binding pockets and the transmembrane domains and allowed for the identification of the sequence of conformational changes associated with the initial steps in this process.

(See Sophia’s recent paper in Structure)

BcompB seminar May 24th: Prof Charles Laughton (Nottingham)

BcompB seminar, Friday May 24th, 2-3pm, C44 (Biomedical Sciences building)

The BcompB seminar in May will be given by Charles (Charlie) Laughton, Professor of Computational Pharmaceutical Science at the University of Nottingham ( https://www.nottingham.ac.uk/pharmacy/people/charles.laughton ).

All welcome!


Enhancing conformational sampling of biomolecules with machine learning and the cloud

Abstract:  I will describe some of our recent research developing new methods for the enhanced sampling of the conformational space of biomolecules, both large and small. I will concentrate on methods that combine molecular dynamics-based sampling with machine learning based supervision in iterative, adaptive, workflows. I will also describe the cloud-based infrastructure and workflow tools we have developed to support this type of research, which we are now making generally available.

BcompB meeting March 19th 2019

BcompB meeting on Molecular Docking

Tuesday March 19th, 2-3pm, C42

During this meeting, we will discuss various aspects molecular docking, including docking small-molecule databases (e.g. to discover lead compounds), protein-protein docking and flexible protein-ligand docking.

With contributions from Richard Sessions, Amaurys Ávila  Ibarra, Debbie Shoemark, Sam Johns and Charlie Colenso, some of the experience in Bristol is highlighted, and indications are given how you can use techniques yourself.

All welcome!


BcompB seminar Jan 15th: Prof Carmen Domene – Studies of TRP channel activation and modulation using computational approaches

The first BcompB meeting in 2019 will be an external seminar from Prof Carmen Domene (University of Bath).

It will take place on Jan 15th, 2-3pm in LT4 in the School of Chemistry.

Carmen is an expert in the structure, dynamics and mechanism of trans-membrane channels, which her group studies through atomistic molecular dynamics simulations, including enhanced sampling techniques (such as metadynamics).

She will give a talk entitled:

“Studies of TRP channel activation and modulation using computational approaches”


Transient receptor potential (TRP) ion channels constitute a notable family of cation channels involved in the ability of organisms to detect noxious mechanical, thermal and chemical stimuli that gives rise to the perception of pain. One of the most experimentally studied agonist of TRP channels is capsaicin, which is responsible for the burning sensation produced when chili pepper is in contact with organic tissues. Understanding how TRP channels are regulated by capsaicin and other natural products is essential to high impact pharmacological applications, particularly those related to pain treatment. By selected examples from the work we have carried out, I will provide an overview of the current knowledge we have about activation, permeation and selectivity of one of these human molecular thermometers.

BcompB seminar 18/09/2018: Dr Richard Sessions

Dr Richard Sessions is the molecular modeller responsible for the development of the docking algorithm BUDE (Bristol University Docking engine), the binding energy prediction method that underpins programs such as CC-builder, Isambard and Poppi.

His talk tomorrow explores the fundamental question, “Why do molecules stick together?”

It will be at 2pm in C42 in the Biomedical Sciences building.


BcompB Seminar: Dr Simon Bennie

Improving the teaching of enzymology using VR

17/07/18 Chemistry LT4 2pm

Dr Simon Bennie from the Glowacki Group will talk about the introduction of multi-user VR technology into Chemistry undergraduate teaching labs. This work was recently awarded the University Educational Initiative Award 2018. Interactive MD simulations in VR have recently been highlighted in the News on Bristol University’s website, Chemistry World and also by the New York Times. There will be the opportunity to try out the VR framework after the seminar.