The diffusion learning method, DiffDock, for docking small-molecule ligands into protein binding sites was recently introduced. Results included comparisons to more conventional docking approaches, with DiffDock showing superior performance. Here, we employ a fully automatic workflow using the Surflex-Dock methods to generate a fair baseline for conventional docking approaches. Results were generated for the common and expected situation where a binding site location is known and also for the condition of an unknown binding site. For the known binding site condition, Surflex-Dock success rates at 2.0 Angstroms RMSD far exceeded those for DiffDock (Top-1/Top-5 success rates, respectively, were 68/81% compared with 45/51%). Glide performed with similar success rates (67/73%) to Surflex-Dock for the known binding site condition, and results for AutoDock Vina and Gnina followed this pattern. For the unknown binding site condition, using an automated method to identify multiple binding pockets, Surflex-Dock success rates again exceeded those of DiffDock, but by a somewhat lesser margin. DiffDock made use of roughly 17,000 co-crystal structures for learning (98% of PDBBind version 2020, pre-2019 structures) for a training set in order to predict on 363 test cases (2% of PDBBind 2020) from 2019 forward. DiffDock's performance was inextricably linked with the presence of near-neighbor cases of close to identical protein-ligand complexes in the training set for over half of the test set cases. DiffDock exhibited a 40 percentage point difference on near-neighbor cases (two-thirds of all test cases) compared with cases with no near-neighbor training case. DiffDock has apparently encoded a type of table-lookup during its learning process, rendering meaningful applications beyond its reach. Further, it does not perform even close to competitively with a competently run modern docking workflow.

Thomas G. Dietterich Arris Pharmaceutical Corporation and Oregon State University Corvallis, OR 97331-3202 Ajay N. Jain Arris Pharmaceutical Corporation 385 Oyster Point Blvd., Suite 3 South San Francisco, CA 94080 Richard H. Lathrop and Tomas Lozano-Perez Arris Pharmaceutical Corporation and MIT Artificial Intelligence Laboratory 545 Technology Square Cambridge, MA 02139 Abstract In drug activity prediction (as in handwritten character recognition), thefeatures extracted to describe a training example depend on the pose (location, orientation, etc.) of the example. In handwritten characterrecognition, one of the best techniques for addressing thisproblem is the tangent distance method of Simard, LeCun and Denker (1993). Jain, et al. (1993a; 1993b) introduce a new technique-dynamic reposing-that also addresses this problem. Dynamicreposing iteratively learns a neural network and then reposes the examples in an effort to maximize the predicted output values.New models are trained and new poses computed until models and poses converge. This paper compares dynamic reposing to the tangent distance method on the task of predicting the biological activityof musk compounds.

The task of drug activity prediction is to predict the activity of proposed drug compounds by learning from the observed activity of previously-synthesized drug compounds. Accurate drug activity prediction can save substantial time and money by focusing the efforts of chemists and biologists on the synthesis and testing of compounds whose predicted activity is high. If the requirements for highly active binding can be displayed in three dimensions, chemists can work from such displays to design new compounds having high predicted activity. Drug molecules usually act by binding to localized sites on large receptor molecules or large enyzme molecules. One reasonable way to represent drug molecules is to capture the location of their surface in the (fixed) frame of reference of the (hypothesized) binding site.

This paper presents PARSECa system for generating connectionist parsing networks from example parses. PARSEC is not based on formal grammar systems and is geared toward spoken language tasks. PARSEC networks exhibit three strengths important for application to speech processing: 1)they learn to parse, and generalize well compared to handcoded grammars; 2) they tolerate several types of noise; 3) they can learn to use multi-modal input. Presented are the PARSEC architecture and performance analyses along several dimensions that demonstrate PARSEC's features. PARSEC's performance is compared to that of traditional grammar-basedparsing systems. 1 INTRODUCTION While a great deal of research has been done developing parsers for natural language, adequate solutionsfor some of the particular problems involved in spoken language have not been found. Among the unsolved problems are the difficulty in constructing task-specific grammars, lack of tolerance to noisy input, and inability to effectively utilize non-symbolic information.This paper describes PARSECa system for generating connectionist parsing networks from example parses.

JANUS translates continuously spoken English and German into German, English, and Japanese.

This paper presents PARSECa system for generating connectionist parsing networks from example parses. PARSEC is not based on formal grammar systems and is geared toward spoken language tasks. PARSEC networks exhibit three strengths important for application to speech processing: 1) they learn to parse, and generalize well compared to handcoded grammars; 2) they tolerate several types of noise; 3) they can learn to use multi-modal input. Presented are the PARSEC architecture and performance analyses along several dimensions that demonstrate PARSEC's features. PARSEC's performance is compared to that of traditional grammar-based parsing systems.

JANUS translates continuously spoken English and German into German, English, and Japanese. JANUS currently achieves 87% translation fidelity from English speech and 97% from German speech. We present the JANUS system along with comparative evaluations of its interchangeable processing components, with special emphasis on the connectionist modules.

We present a novel, modular, recurrent connectionist network architecture which learns to robustly perform incremental parsing of complex sentences. From sequential input, one word at a time, our networks learn to do semantic role assignment, noun phrase attachment, and clause structure recognition for sentences with passive constructions and center embedded clauses. The networks make syntactic and semantic predictions at every point in time, and previous predictions are revised as expectations are affirmed or violated with the arrival of new information. Our networks induce their own "grammar rules" for dynamically transforming an input sequence of words into a syntactic/semantic interpretation. These networks generalize and display tolerance to input which has been corrupted in ways common in spoken language.

We present a novel, modular, recurrent connectionist network architecture which learns to robustly perform incremental parsing of complex sentences. From sequential input, one word at a time, our networks learn to do semantic role assignment, noun phrase attachment, and clause structure recognition for sentences with passive constructions and center embedded clauses. The networks make syntactic and semantic predictions at every point in time, and previous predictions are revised as expectations are affirmed or violated with the arrival of new information. Our networks induce their own "grammar rules" for dynamically transforming an input sequence of words into a syntactic/semantic interpretation. These networks generalize and display tolerance to input which has been corrupted in ways common in spoken language.

We present a novel, modular, recurrent connectionist network architecture of complexwhich learns to robustly perform incremental parsing sentences. From sequential input, one word at a time, our networks learn to do semantic role assignment, noun phrase attachment, and clause structure recognition for sentences with passive constructions and center embedded clauses. The networks make syntactic and semantic predictions at every point in time, and previous predictions are revised as expectations are affirmed or violated with the arrival of new information. Our networks induce their own "grammar rules" for dynamically transforming an input sequence of words into a syntactic/semantic interpretation.