Evaluation of multiple protein docking structures using correctly predicted pairwise subunits

<p>Abstract</p> <p>Background</p> <p>Many functionally important proteins in a cell form complexes with multiple chains. Therefore, computational prediction of multiple protein complexes is an important task in bioinformatics. In the development of multiple protein docking methods, it is important to establish a metric for evaluating prediction results in a reasonable and practical fashion. However, since there are only few works done in developing methods for multiple protein docking, there is no study that investigates how accurate structural models of multiple protein complexes should be to allow scientists to gain biological insights.</p> <p>Methods</p> <p>We generated a series of predicted models (decoys) of various accuracies by our multiple protein docking pipeline, Multi-LZerD, for three multi-chain complexes with 3, 4, and 6 chains. We analyzed the decoys in terms of the number of correctly predicted pair conformations in the decoys.</p> <p>Results and conclusion</p> <p>We found that pairs of chains with the correct mutual orientation exist even in the decoys with a large overall root mean square deviation (RMSD) to the native. Therefore, in addition to a global structure similarity measure, such as the global RMSD, the quality of models for multiple chain complexes can be better evaluated by using the local measurement, the number of chain pairs with correct mutual orientation. We termed the fraction of correctly predicted pairs (RMSD at the interface of less than 4.0Å) as <it>fpair </it>and propose to use it for evaluation of the accuracy of multiple protein docking.</p

Spherical harmonics coeffcients for ligand-based virtual screening of cyclooxygenase inhibitors

Background: Molecular descriptors are essential for many applications in computational chemistry, such as ligand-based similarity searching. Spherical harmonics have previously been suggested as comprehensive descriptors of molecular structure and properties. We investigate a spherical harmonics descriptor for shape-based virtual screening. Methodology/Principal Findings: We introduce and validate a partially rotation-invariant three-dimensional molecular shape descriptor based on the norm of spherical harmonics expansion coefficients. Using this molecular representation, we parameterize molecular surfaces, i.e., isosurfaces of spatial molecular property distributions. We validate the shape descriptor in a comprehensive retrospective virtual screening experiment. In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. Conclusions/Significance: 12 compounds were tested in vitro for direct enzyme inhibition and in a whole blood assay. Active compounds containing a triazole scaffold were identified as direct cyclooxygenase-1 inhibitors. This outcome corroborates the usefulness of spherical harmonics for representation of molecular shape in virtual screening of large compound collections. The combination of pharmacophore and shape-based filtering of screening candidates proved to be a straightforward approach to finding novel bioactive chemotypes with minimal experimental effort

SHREC'08 entry: Training set expansion via autotags

Training a 3D model classifier on a small dataset is very challenging. However, large datasets of partially classified models are now commonly available online. We use an external training set of models with associated text tags to automatically assign tags to both training and query models. The similarity between these tags, used in conjunction with a standard shape descriptor, yields a multiclassifier that outperforms the standalone shape descriptor

Continuous and Optimally Complete Description of Chemical Environments Using Spherical Bessel Descriptors

Recently, machine learning potentials have been advanced as candidates to combine the high-accuracy of quantum mechanical simulations with the speed of classical interatomic potentials. A crucial component of a machine learning potential is the description of local atomic environments by some set of descriptors. These should ideally be continuous throughout the specified local atomic environment, twice-differentiable with respect to atomic positions and complete in the sense of containing all possible information about the neighborhood. An updated version of the recently proposed Spherical Bessel descriptors satisfies all three of these properties, and moreover is optimally complete in the sense of encoding all configurational information with the smallest possible number of descriptors. The Smooth Overlap of Atomic Position descriptors that are frequently visited in the literature and the Zernike descriptors that are built upon a similar basis are included into the discussion as being the natural counterparts of the Spherical Bessel descriptors, and shown to be incapable of satisfying the full list of core requirements for an accurate description. Aside being mathematically and physically superior, the Spherical Bessel descriptors have also the advantage of allowing machine learning potentials of comparable accuracy that require roughly an order of magnitude less computation time per evaluation than the Smooth Overlap of Atomic Position descriptors, which appear to be the common choice of descriptors in recent studies.Comment: 15 pages, 5 figures, under review for Journal of Chemical Physic

The Columbia Grasp Database

Collecting grasp data for learning and benchmarking purposes is very expensive. It would be helpful to have a standard database of graspable objects, along with a set of stable grasps for each object, but no such database exists. In this work we show how to automate the construction of a database consisting of several hands, thousands of objects, and hundreds of thousands of grasps. Using this database, we demonstrate a novel grasp planning algorithm that exploits geometric similarity between a 3D model and the objects in the database to synthesize form closure grasps. Our contributions are this algorithm, and the database itself, which we are releasing to the community as a tool for both grasp planning and benchmarking

Robust designs for 3D shape analysis with spherical harmonic descriptors

--

Optimal designs for three-dimensional shape analysis with spherical harmonic descriptors

We determine optimal designs for some regression models which are frequently used for describing three-dimensional shapes. These models are based on a Fourier expansion of a function defined on the unit sphere in terms of spherical harmonic basis functions. In particular, it is demonstrated that the uniform distribution on the sphere is optimal with respect to all $\Phi_p$ criteria proposed by Kiefer in 1974 and also optimal with respect to a criterion which maximizes a $p$ mean of the $r$ smallest eigenvalues of the variance--covariance matrix. This criterion is related to principal component analysis, which is the common tool for analyzing this type of image data. Moreover, discrete designs on the sphere are derived, which yield the same information matrix in the spherical harmonic regression model as the uniform distribution and are therefore directly implementable in practice. It is demonstrated that the new designs are substantially more efficient than the commonly used designs in three-dimensional shape analysis.Comment: Published at http://dx.doi.org/10.1214/009053605000000552 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org