Search arXivSearch

arXiv · 2202.11752

Analysis of Coronavirus Envelope Protein with Cellular Automata (CA) Model

Abstract

The reason of significantly higher transmissibility of SARS Covid (2019 CoV-2) compared to SARS Covid (2003 CoV) and MERS Covid (2012 MERS) can be attributed to mutations reported in structural proteins, and the role played by non-structural proteins (nsps) and accessory proteins (ORFs) for viral replication, assembly, and shedding. Envelope protein E is one of the four structural proteins of minimum length. Recent studies have confirmed critical role played by the envelope protein in the viral life cycle including assembly of virion exported from infected cell for its transmission. However, the determinants of the highly complex viral - host interactions of envelope protein, particularly with host Golgi complex, have not been adequately characterized. CoV-2 and CoV Envelope proteins of length 75 and 76 amino acids differ in four amino acid locations. The additional amino acid Gly (G) at location 70 makes CoV length 76. The amino acid pair EG at location 69-70 of CoV in place of amino acid R in location 69 of CoV-2, has been identified as a major determining factor in the current investigation. This paper concentrates on the design of computational model to compare the structure/function of wild and mutants of CoV-2 with wild and mutants of CoV in the functionally important region of the protein chain pair. We hypothesize that differences of CAML model parameter of CoV-2 and CoV characterize the deviation in structure and function of envelope proteins in respect of interaction of virus with host Golgi complex; and this difference gets reflected in the difference of their transmissibility. The hypothesis has been validated from single point mutational study on- (i) human HBB beta-globin hemoglobin protein associated with sickle cell anemia, (ii) mutants of envelope protein of Covid-2 infected patients reported in recent publications.

Explore related subjects

Keep this discovery

BibTeXRIS

Raju Hazari, P Pal Chaudhuri. 2022-01-15. Analysis of Coronavirus Envelope Protein with Cellular Automata (CA) Model. https://arxiv.org/abs/2202.11752

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

Sequence-Informed Geometric Evaluation of RNA 3D Structures

Computational RNA structure pipelines generate many candidate conformations for the same sequence. Reliable evaluation therefore requires more than recognising plausible geometry, it requires determining whether that geometry is compatible with the sequence. We introduce SIRGE, a sequence-informed geometric evaluator that conditions structural representations on nucleotide embeddings from a pretrained RNA language model. Early results show that SIRGE outperforms established evaluators in Kendall--$\tau$ alignment, Top-1 selection, and Top-3 ranking. Controlled comparisons further show that sequence conditioning corrects errors made by an otherwise matched geometric model and improves target-level rank structure. These findings provide initial evidence that pretrained sequence representations supply ranking information that complements geometric reasoning.

q-bio.BM

PocketVE: Stable and Property-Guided Structure-Based Drug Design with Variance-Exploding Diffusion

Protein-conditioned 3D molecule generation is a central challenge in structure-based drug design, requiring a balance between pocket compatibility, molecular properties, and physical geometry. We propose \textbf{PocketVE}, a protein-pocket-conditioned variance-exploding (VE) diffusion framework that couples stable coordinate denoising with inference-time property guidance. Specifically, PocketVE combines an EDM-style training and sampling setup for 3D denoising, classifier-free guidance for multi-property steering without external property classifiers, and adaptive protein perturbation as a training-time pocket regularizer. Evaluated on CrossDocked2020 under the GenBench3D protocol, PocketVE improves Valid$_{3\text{D}}$ from 58.6 to 80.6 and reduces strain energy from 457.4 to 127.9 relative to its TAGMol architectural baseline, while retaining competitive docking and molecular-property scores under moderate guidance. A guidance-scale study shows that moderate guidance gives a favorable balance between target-related objectives and geometric quality, whereas stronger guidance can degrade geometry and distributional fidelity. Pocket-permutation and PoseCheck diagnostics further support pocket-specific spatial compatibility with reduced steric conflicts. Overall, the results suggest that geometric stability and inference-time property guidance should be considered as coupled design objectives.

q-bio.BM

Predicting directional flexibility in proteins

Predicting protein dynamics is a long-standing problem in computational structural biology. Often, protein function critically depends on local directed motions, such as hinge movements, catalytic loop rearrangements and domain reorientations, which can be characterized by directional flexibility and correlated structural motions of the protein backbone. While Molecular Dynamics (MD) simulations provide an established but often prohibitively expensive approach, recent deep generative models aim to reduce this cost by directly predicting conformational ensembles, emulating MD. However, due to their large size and the need to generate several states until the derived dynamical properties converge, these models remain expensive. In this work, we propose BackFlip-2: a fast SE(3)-equivariant graph neural network trained to directly predict dynamical descriptors, such as directional backbone flexibility and pairwise dynamic correlations, from an equilibrium structure. In a series of experiments, we show that our model matches the accuracy of substantially larger ensemble generation models while being orders of magnitude faster, and demonstrate that the proposed equivariant architecture is especially well-suited for capturing anisotropic motions in proteins. BackFlip-2 model weights, training and inference code are available at https://github.com/graeter-group/backflip.

q-bio.BM