Computational structure‐based drug design: Predicting target flexibility

The role of molecular modeling in drug design has experienced a significant revamp in the last decade. The increase in computational resources and molecular models, along with software developments, is finally introducing a competitive advantage in early phases of drug discovery. Medium and small companies with strong focus on computational chemistry are being created, some of them having introduced important leads in drug design pipelines. An important source for this success is the extraordinary development of faster and more efficient techniques for describing flexibility in three‐dimensional structural molecular modeling. At different levels, from docking techniques to atomistic molecular dynamics, conformational sampling between receptor and drug results in improved predictions, such as screening enrichment, discovery of transient cavities, etc. In this review article we perform an extensive analysis of these modeling techniques, dividing them into high and low throughput, and emphasizing in their application to drug design studies. We finalize the review with a section describing our Monte Carlo method, PELE, recently highlighted as an outstanding advance in an international blind competition and industrial benchmarks.We acknowledge the BSC-CRG-IRB Joint Research Program in Computational Biology. This work was supported by a grant from the Spanish Government CTQ2016-79138-R.J.I. acknowledges support from SVP-2014-068797, awarded by the Spanish Government.Peer ReviewedPostprint (author's final draft

Learning to Reconstruct Shapes from Unseen Classes

From a single image, humans are able to perceive the full 3D shape of an object by exploiting learned shape priors from everyday life. Contemporary single-image 3D reconstruction algorithms aim to solve this task in a similar fashion, but often end up with priors that are highly biased by training classes. Here we present an algorithm, Generalizable Reconstruction (GenRe), designed to capture more generic, class-agnostic shape priors. We achieve this with an inference network and training procedure that combine 2.5D representations of visible surfaces (depth and silhouette), spherical shape representations of both visible and non-visible surfaces, and 3D voxel-based representations, in a principled manner that exploits the causal structure of how 3D shapes give rise to 2D images. Experiments demonstrate that GenRe performs well on single-view shape reconstruction, and generalizes to diverse novel objects from categories not seen during training.Comment: NeurIPS 2018 (Oral). The first two authors contributed equally to this paper. Project page: http://genre.csail.mit.edu

Sequential non-rigid structure from motion using physical priors

© 20xx IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.We propose a new approach to simultaneously recover camera pose and 3D shape of non-rigid and potentially extensible surfaces from a monocular image sequence. For this purpose, we make use of the Extended Kalman Filter based Simultaneous Localization And Mapping (EKF-SLAM) formulation, a Bayesian optimization framework traditionally used in mobile robotics for estimating camera pose and reconstructing rigid scenarios. In order to extend the problem to a deformable domain we represent the object's surface mechanics by means of Navier's equations, which are solved using a Finite Element Method (FEM). With these main ingredients, we can further model the material's stretching, allowing us to go a step further than most of current techniques, typically constrained to surfaces undergoing isometric deformations. We extensively validate our approach in both real and synthetic experiments, and demonstrate its advantages with respect to competing methods. More specifically, we show that besides simultaneously retrieving camera pose and non-rigid shape, our approach is adequate for both isometric and extensible surfaces, does not require neither batch processing all the frames nor tracking points over the whole sequence and runs at several frames per second.Peer ReviewedPostprint (author's final draft

Real-time 3D reconstruction of non-rigid shapes with a single moving camera

© . This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/This paper describes a real-time sequential method to simultaneously recover the camera motion and the 3D shape of deformable objects from a calibrated monocular video. For this purpose, we consider the Navier-Cauchy equations used in 3D linear elasticity and solved by finite elements, to model the time-varying shape per frame. These equations are embedded in an extended Kalman filter, resulting in sequential Bayesian estimation approach. We represent the shape, with unknown material properties, as a combination of elastic elements whose nodal points correspond to salient points in the image. The global rigidity of the shape is encoded by a stiffness matrix, computed after assembling each of these elements. With this piecewise model, we can linearly relate the 3D displacements with the 3D acting forces that cause the object deformation, assumed to be normally distributed. While standard finite-element-method techniques require imposing boundary conditions to solve the resulting linear system, in this work we eliminate this requirement by modeling the compliance matrix with a generalized pseudoinverse that enforces a pre-fixed rank. Our framework also ensures surface continuity without the need for a post-processing step to stitch all the piecewise reconstructions into a global smooth shape. We present experimental results using both synthetic and real videos for different scenarios ranging from isometric to elastic deformations. We also show the consistency of the estimation with respect to 3D ground truth data, include several experiments assessing robustness against artifacts and finally, provide an experimental validation of our performance in real time at frame rate for small mapsPeer ReviewedPostprint (author's final draft

Planning and Real Time Control of a Minimally Invasive Robotic Surgery System

This paper introduces the planning and control software of a teleoperating robotic system for minimally invasive surgery. It addresses the problem of how to organize a complex system with 41 degrees of freedom including robot setup planning, force feedback control and nullspace handling with three robotic arms. The planning software is separated into sequentially executed planning and registration procedures. An optimal setup is first planned in virtual reality and then adapted to variations in the operating room. The real time control system is composed of hierarchical layers. The design is flexible and expandable without losing performance. Structure, functionality and implementation of planning and control are described. The robotic system provides the surgeon with an intuitive hand-eye-coordination and force feedback in teleoperation for both hands

Spatial calibration of an optical see-through head-mounted display

We present here a method for calibrating an optical see-through Head Mounted Display (HMD) using techniques usually applied to camera calibration (photogrammetry). Using a camera placed inside the HMD to take pictures simultaneously of a tracked object and features in the HMD display, we could exploit established camera calibration techniques to recover both the intrinsic and extrinsic properties of the~HMD (width, height, focal length, optic centre and principal ray of the display). Our method gives low re-projection errors and, unlike existing methods, involves no time-consuming and error-prone human measurements, nor any prior estimates about the HMD geometry