MANORAA: A machine learning platform to guide protein-ligand design by anchors and influential distances.

The MANORAA platform uses structure-based approaches to provide information on drug design originally derived from mapping tens of thousands of amino acids on a grid. In-depth analyses of the pockets, frequently occurring atoms, influential distances, and active-site boundaries are used for the analysis of active sites. The algorithms derived provide model equations that can predict whether changes in distances, such as contraction or expansion, will result in improved binding affinity. The algorithm is confirmed using kinetic studies of dihydrofolate reductase (DHFR), together with two DHFR-TS crystal structures. Empirical analyses of 881 crystal structures involving 180 ligands are used to interpret protein-ligand binding affinities. MANORAA links to major biological databases for web-based analysis of drug design. The frequency of atoms inside the main protease structures, including those from SARS-CoV-2, shows how the rigid part of the ligand can be used as a probe for molecular design (http://manoraa.org).

MANORAA (Mapping Analogous Nuclei Onto Residue And Affinity) for identifying protein-ligand fragment interaction, pathways and SNPs.

Protein-ligand interaction analysis is an important step of drug design and protein engineering in order to predict the binding affinity and selectivity between ligands to the target proteins. To date, there are more than 100 000 structures available in the Protein Data Bank (PDB), of which ∼30% are protein-ligand (MW below 1000 Da) complexes. We have developed the integrative web server MANORAA (Mapping Analogous Nuclei Onto Residue And Affinity) with the aim of providing a user-friendly web interface to assist structural study and design of protein-ligand interactions. In brief, the server allows the users to input the chemical fragments and present all the unique molecular interactions to the target proteins with available three-dimensional structures in the PDB. The users can also link the ligands of interest to assess possible off-target proteins, human variants and pathway information using our all-in-one integrated tools. Taken together, we envisage that the server will facilitate and improve the study of protein-ligand interactions by allowing observation and comparison of ligand interactions with multiple proteins at the same time. (http://manoraa.org).

ExpertEyes: open-source, high-definition eyetracking.

ExpertEyes is a low-cost, open-source package of hardware and software that is designed to provide portable high-definition eyetracking. The project involves several technological innovations, including portability, high-definition video recording, and multiplatform software support. It was designed for challenging recording environments, and all processing is done offline to allow for optimization of parameter estimation. The pupil and corneal reflection are estimated using a novel forward eye model that simultaneously fits both the pupil and the corneal reflection with full ellipses, addressing a common situation in which the corneal reflection sits at the edge of the pupil and therefore breaks the contour of the ellipse. The accuracy and precision of the system are comparable to or better than what is available in commercial eyetracking systems, with a typical accuracy of less than 0.4° and best accuracy below 0.3°, and with a typical precision (SD method) around 0.3° and best precision below 0.2°. Part of the success of the system comes from a high-resolution eye image. The high image quality results from uncasing common digital camcorders and recording directly to SD cards, which avoids the limitations of the analog NTSC format. The software is freely downloadable, and complete hardware plans are available, along with sources for custom parts.

Toward mobile 3D visualization for structural biologists.

Technological advances in crystallography have led to the ever-rapidly increasing number of biomolecular structures deposited in public repertoires. This undoubtedly shifts the bottleneck of structural biology research from obtaining high-quality structures to data analysis and interpretation. The recently available glasses-free autostereoscopic laptop offers an unprecedented opportunity to visualize and study 3D structures using a much more affordable, and for the first time, portable device. Together with a gamepad re-programmed for 3D structure controlling, we describe how the gaming technologies can deliver the output 3D images for high-quality viewing, comparable to that of a passive stereoscopic system, and can give the user more control and flexibility than the conventional controlling setup using only a mouse and a keyboard.