Locating binding poses in protein-ligand systems using reconnaissance metadynamics

A molecular dynamics-based protocol is proposed for finding and scoring protein-ligand binding poses. This protocol uses the recently developed reconnaissance metadynamics method, which employs a self-learning algorithm to construct a bias that pushes the system away from the kinetic traps where it would otherwise remain. The exploration of phase space with this algorithm is shown to be roughly six to eight times faster than unbiased molecular dynamics and is only limited by the time taken to diffuse about the surface of the protein. We apply this method to the well-studied trypsin-benzamidine system and show that we are able to refind all the poses obtained from a reference EADock blind docking calculation. These poses can be scored based on the length of time the system remains trapped in the pose. Alternatively, one can perform dimensionality reduction on the output trajectory and obtain a map of phase space that can be used in more expensive free-energy calculations.

Intrusion Detection System for Network Security in Synchrophasor Systems

Synchrophasor systems will play a crucial role in next generation Smart Grid monitoring, protection and control. However these systems also introduce a multitude of potential vulnerabilities from malicious and inadvertent attacks, which may render erroneous operation or severe damage. This paper proposes a Synchrophasor Specific Intrusion Detection System (SSIDS) for malicious cyber attack and unintended misuse. The SSIDS comprises a heterogeneous whitelist and behavior-based approach to detect known attack types and unknown and so-called ‘zero-day’ vulnerabilities and attacks. The paper describes reconnaissance, Man-in-the-Middle (MITM) and Denial-of-Service (DoS) attack types executed against a practical synchrophasor system which are used to validate the real-time effectiveness of the proposed SSIDS cyber detection method.