Parameter Optimization for Interaction between C-Terminal Domains of HIV-1 Capsid Protein

HIV-1 capsid proteins (CAs) assemble into a capsid that encloses the viral RNA. The binding between a pair of C-terminal domains (CTDs) constitutes a major interface in both the CA dimers and the large CA assemblies. Here, we attempt to use a general residue-level coarse-grained model to describe the interaction between two isolated CTDs in Monte Carlo simulations. With the standard parameters that depend only on the residue types, the model predicts a much weaker binding in comparison to the experiments. Detailed analysis reveals that some Lennard-Jones parameters are not compatible with the experimental CTD dimer structure, thus resulting in an unfavorable interaction energy. To improve the model for the CTD binding, we introduce ad hoc modifications to a small number of Lennard-Jones parameters for some specific pairs of residues at the binding interface. Through a series of extensive Monte Carlo simulations, we identify the optimal parameters for the CTD–CTD interactions. With the refined model parameters, both the binding affinity (with a dissociation constant of 13 ± 2 μM) and the binding mode are in good agreement with the experimental data. This study demonstrates that the general interaction model based on the Lennard-Jones potential, with some modest adjustment of the parameters for key residues, could correctly reproduce the reversible protein binding, thus potentially applicable for simulating the thermodynamics of the CA assemblies

Harnessing the Plug-and-Play Controller by Prompting

Controllable text generation is a growing field within natural language generation (NLG) that focuses on producing text that meets specific constraints in real-world applications. Previous approaches, such as plug-and-play controllers (PPCs), aimed to steer the properties of generated text in a flexible manner. However, these methods often compromised the integrity of the language model's decoding process, resulting in less smooth text generation. Alternatively, other techniques utilized multiple attribute prompts to align the generated text with desired attributes, but this approach required prompt design for each attribute and was dependent on the size of the language model. This paper introduces a novel method for flexible attribute control in text generation using pre-trained language models (PLMs). The proposed approach aims to enhance the fluency of generated text by guiding the generation process with PPCs. The key idea is to dynamically adjust the distribution of generated text by modifying prompts, effectively constraining the output space of the language model and influencing the desired attribute. To enable smooth cooperation between the PLM and the PPC, our work innovatively proposes a new model fine-tuning method: Reinforcement Learning with Dynamic Adjust Feedback (RLDAF).This fine-tuning process adapts a small subset of the language model's parameters based on the generating actions taken during the PPC control process. The resulting harmonious collaboration between the PLM and PPC leads to improved smoothness in text generation during inference. Extensive experiments were conducted on the SST2 dataset, and the proposed method outperformed previous approaches in various evaluation metrics, including text fluency and attribute consistency.Comment: The Third Version of the Generation, Evaluation & Metrics (GEM) Workshop in EMNLP 202

Solving Prediction Problems from Temporal Event Data on Networks

Indiana University-Purdue University Indianapolis (IUPUI)Many complex processes can be viewed as sequential events on a network. In this thesis, we study the interplay between a network and the event sequences on it. We first focus on predicting events on a known network. Examples of such include: modeling retweet cascades, forecasting earthquakes, and tracing the source of a pandemic. In specific, given the network structure, we solve two types of problems - (1) forecasting future events based on the historical events, and (2) identifying the initial event(s) based on some later observations of the dynamics. The inverse problem of inferring the unknown network topology or links, based on the events, is also of great important. Examples along this line include: constructing influence networks among Twitter users from their tweets, soliciting new members to join an event based on their participation history, and recommending positions for job seekers according to their work experience. Following this direction, we study two types of problems - (1) recovering influence networks, and (2) predicting links between a node and a group of nodes, from event sequences

Magnons in Ferromagnetic Metallic Manganites

Ferromagnetic (FM) manganites, a group of likely half-metallic oxides, are of special interest not only because they are a testing ground of the classical doubleexchange interaction mechanism for the colossal magnetoresistance, but also because they exhibit an extraordinary arena of emergent phenomena. These emergent phenomena are related to the complexity associated with strong interplay between charge, spin, orbital, and lattice. In this review, we focus on the use of inelastic neutron scattering to study the spin dynamics, mainly the magnon excitations in this class of FM metallic materials. In particular, we discussed the unusual magnon softening and damping near the Brillouin zone boundary in relatively narrow band compounds with strong Jahn-Teller lattice distortion and charge/orbital correlations. The anomalous behaviors of magnons in these compounds indicate the likelihood of cooperative excitations involving spin, lattice, as well as orbital degrees of freedom.Comment: published in J. Phys.: Cond. Matt. 20 figure

Testing gene-environment interactions for rare and/or common variants in sequencing association studies.

The risk of many complex diseases is determined by a complex interplay of genetic and environmental factors. Advanced next generation sequencing technology makes identification of gene-environment (GE) interactions for both common and rare variants possible. However, most existing methods focus on testing the main effects of common and/or rare genetic variants. There are limited methods developed to test the effects of GE interactions for rare variants only or rare and common variants simultaneously. In this study, we develop novel approaches to test the effects of GE interactions of rare and/or common risk, and/or protective variants in sequencing association studies. We propose two approaches: 1) testing the effects of an optimally weighted combination of GE interactions for rare variants (TOW-GE); 2) testing the effects of a weighted combination of GE interactions for both rare and common variants (variable weight TOW-GE, VW-TOW-GE). Extensive simulation studies based on the Genetic Analysis Workshop 17 data show that the type I error rates of the proposed methods are well controlled. Compared to the existing interaction sequence kernel association test (ISKAT), TOW-GE is more powerful when there are GE interactions\u27 effects for rare risk and/or protective variants; VW-TOW-GE is more powerful when there are GE interactions\u27 effects for both rare and common risk and protective variants. Both TOW-GE and VW-TOW-GE are robust to the directions of effects of causal GE interactions. We demonstrate the applications of TOW-GE and VW-TOW-GE using an imputed data from the COPDGene Study