Schrödinger

About: Schrödinger is a based out in . It is known for research contribution in the topics: Sputtering & Ion. The organization has 1621 authors who have published 2200 publications receiving 81554 citations.

AggScore: Prediction of aggregation-prone regions in proteins based on the distribution of surface patches.

Abstract: Protein aggregation is a phenomenon that has attracted considerable attention within the pharmaceutical industry from both a developability standpoint (to ensure stability of protein formulations) and from a research perspective for neurodegenerative diseases. Experimental identification of aggregation behavior in proteins can be expensive; and hence, the development of accurate computational approaches is crucial. The existing methods for predicting protein aggregation rely mostly on the primary sequence and are typically trained on amyloid-like proteins. However, the training bias toward beta amyloid peptides may worsen prediction accuracy of such models when applied to larger protein systems. Here, we present a novel algorithm to identify aggregation-prone regions in proteins termed "AggScore" that is based entirely on three-dimensional structure input. The method uses the distribution of hydrophobic and electrostatic patches on the surface of the protein, factoring in the intensity and relative orientation of the respective surface patches into an aggregation propensity function that has been trained on a benchmark set of 31 adnectin proteins. AggScore can accurately identify aggregation-prone regions in several well-studied proteins and also reliably predict changes in aggregation behavior upon residue mutation. The method is agnostic to an amyloid-specific aggregation context and thus may be applied to globular proteins, small peptides and antibodies.

Analysis of foliar uptake of pesticides in barley leaves: Role of epicuticular waxes and compartmentation

Abstract: Uptake of pesticides into barley leaves was measured under controlled conditions. Leaves detached from plants were submerged in aqueous solutions of 14C-labelled (2,4-dichlorophenoxy)acetic acid, triadimenol, bitertanol and pentachlorophenol. Uptake was biphasic. A short (30-min) period with high rates of uptake was followed by uptake that proceeded more slowly and was steady over hours. Compartmentation of pesticides was studied by desorbing pentachlorophenol from leaves previously loaded with [14C]pentachlorophenol. From the uptake and desorption kinetics it was concluded that penetration of pesticides proceeds as follows: the compounds are first sorbed at the surface of epicuticular wax aggregates where they are in contact with the donor solutions. Solutes then diffuse through the surface wax aggregates into the cuticle. Equilibrium between donor solutions, surface wax and cuticle is established in about 30 min. After this time the amounts of solutes in these compartments no longer increase. Uptake after this time represents penetration into the leaf cells. This fraction of the pentachlorophenol is retained irreversibly, while that sorbed in wax and cutin can be desorbed again. All compounds were sorbed in cuticular waxes and partition coefficients wax/water were determined. On a mass basis only 5 to 10% of the amounts sorbed in cutin are sorbed in wax. This comparatively low solubility in wax contributes to the barrier properties of cuticular waxes. The other determinant of permeability is the very low mobility of solutes in cuticular waxes.

Reaction-Based Enumeration, Active Learning, and Free Energy Calculations To Rapidly Explore Synthetically Tractable Chemical Space and Optimize Potency of Cyclin-Dependent Kinase 2 Inhibitors.

Abstract: The hit-to-lead and lead optimization processes usually involve the design, synthesis, and profiling of thousands of analogs prior to clinical candidate nomination. A hit finding campaign may begin...

On Fourier Transforms of Radial Functions and Distributions

Abstract: We find a formula that relates the Fourier transform of a radial function on Rn with the Fourier transform of the same function defined on Rn+2. This formula enables one to explicitly calculate the Fourier transform of any radial function f(r) in any dimension, provided one knows the Fourier transform of the one-dimensional function t↦f(|t|) and the two-dimensional function (x1,x2)↦f(|(x1,x2)|). We prove analogous results for radial tempered distributions.

Qualitative behaviour of stochastic delay equations with a bounded memory

Abstract: A dichotomy is proved concerning recurrence properties of the solution of certain stochastic delay equations. If the solution process is recurrent, there exists an invariant measure π on the state space C which is unique (up to a multiplicative constant) and the tail-field is trivial. If π happens to be a probability measure, then for every initial condition, the distribution of the process converges to it as t→∞. We will formulate a sufficient condition for the existence of an invariant probability measure (ipm) in icrnia of Lyapunov junctionals and give two examples, one Heing the stochastic-delay version of the famous logistic equation of population growth. Finally we study approximations of delay equations by Markov chains.