skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Atom-specific persistent homology and its application to protein flexibility analysis
Abstract Recently, persistent homology has had tremendous success in biomolecular data analysis. It works by examining the topological relationship or connectivity of a group of atoms in a molecule at a variety of scales, then rendering a family of topological representations of the molecule. However, persistent homology is rarely employed for the analysis of atomic properties, such as biomolecular flexibility analysis or B-factor prediction. This work introduces atom-specific persistent homology to provide a local atomic level representation of a molecule via a global topological tool. This is achieved through the construction of a pair of conjugated sets of atoms and corresponding conjugated simplicial complexes, as well as conjugated topological spaces. The difference between the topological invariants of the pair of conjugated sets is measured by Bottleneck and Wasserstein metrics and leads to an atom-specific topological representation of individual atomic properties in a molecule. Atom-specific topological features are integrated with various machine learning algorithms, including gradient boosting trees and convolutional neural network for protein thermal fluctuation analysis and B-factor prediction. Extensive numerical results indicate the proposed method provides a powerful topological tool for analyzing and predicting localized information in complex macromolecules.  more » « less
Award ID(s):
1900473 1761320 1721024
PAR ID:
10170693
Author(s) / Creator(s):
;
Date Published:
Journal Name:
Computational and Mathematical Biophysics
Volume:
8
Issue:
1
ISSN:
2544-7297
Page Range / eLocation ID:
1 to 35
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; (, npj Computational Materials)
    null (Ed.)
    Abstract Accurate theoretical predictions of desired properties of materials play an important role in materials research and development. Machine learning (ML) can accelerate the materials design by building a model from input data. For complex datasets, such as those of crystalline compounds, a vital issue is how to construct low-dimensional representations for input crystal structures with chemical insights. In this work, we introduce an algebraic topology-based method, called atom-specific persistent homology (ASPH), as a unique representation of crystal structures. The ASPH can capture both pairwise and many-body interactions and reveal the topology-property relationship of a group of atoms at various scales. Combined with composition-based attributes, ASPH-based ML model provides a highly accurate prediction of the formation energy calculated by density functional theory (DFT). After training with more than 30,000 different structure types and compositions, our model achieves a mean absolute error of 61 meV/atom in cross-validation, which outperforms previous work such as Voronoi tessellations and Coulomb matrix method using the same ML algorithm and datasets. Our results indicate that the proposed topology-based method provides a powerful computational tool for predicting materials properties compared to previous works. 
    more » « less
  2. ; ; (, International Journal for Numerical Methods in Biomedical Engineering)
    Abstract Persistent homology is constrained to purely topological persistence, while multiscale graphs account only for geometric information. This work introduces persistent spectral theory to create a unified low‐dimensional multiscale paradigm for revealing topological persistence and extracting geometric shapes from high‐dimensional datasets. For a point‐cloud dataset, a filtration procedure is used to generate a sequence of chain complexes and associated families of simplicial complexes and chains, from which we construct persistent combinatorial Laplacian matrices. We show that a full set of topological persistence can be completely recovered from the harmonic persistent spectra, that is, the spectra that have zero eigenvalues, of the persistent combinatorial Laplacian matrices. However, non‐harmonic spectra of the Laplacian matrices induced by the filtration offer another powerful tool for data analysis, modeling, and prediction. In this work, fullerene stability is predicted by using both harmonic spectra and non‐harmonic persistent spectra, while the latter spectra are successfully devised to analyze the structure of fullerenes and model protein flexibility, which cannot be straightforwardly extracted from the current persistent homology. The proposed method is found to provide excellent predictions of the protein B‐factors for which current popular biophysical models break down. 
    more » « less
  3. ; (, International Journal for Numerical Methods in Biomedical Engineering)
    Abstract Protein‐ligand binding is a fundamental biological process that is paramount to many other biological processes, such as signal transduction, metabolic pathways, enzyme construction, cell secretion, and gene expression. Accurate prediction of protein‐ligand binding affinities is vital to rational drug design and the understanding of protein‐ligand binding and binding induced function. Existing binding affinity prediction methods are inundated with geometric detail and involve excessively high dimensions, which undermines their predictive power for massive binding data. Topology provides the ultimate level of abstraction and thus incurs too much reduction in geometric information. Persistent homology embeds geometric information into topological invariants and bridges the gap between complex geometry and abstract topology. However, it oversimplifies biological information. This work introduces element specific persistent homology (ESPH) or multicomponent persistent homology to retain crucial biological information during topological simplification. The combination of ESPH and machine learning gives rise to a powerful paradigm for macromolecular analysis. Tests on 2 large data sets indicate that the proposed topology‐based machine‐learning paradigm outperforms other existing methods in protein‐ligand binding affinity predictions. ESPH reveals protein‐ligand binding mechanism that can not be attained from other conventional techniques. The present approach reveals that protein‐ligand hydrophobic interactions are extended to 40Å  away from the binding site, which has a significant ramification to drug and protein design. 
    more » « less
  4. ; (, 2019 IEEE International Conference on Big Data)
    Persistent homology is a method of data analysis that is based in the mathematical field of topology. Unfortunately, the run-time and memory complexities associated with computing persistent homology inhibit general use for the analysis of big data. For example, the best tools currently available to compute persistent homology can process only a few thousand data points in R^3. Several studies have proposed using sampling or data reduction methods to attack this limit. While these approaches enable the computation of persistent homology on much larger data sets, the methods are approximate. Furthermore, while they largely preserve the results of large topological features, they generally miss reporting information about the small topological features that are present in the data set. While this abstraction is useful in many cases, there are data analysis needs where the smaller features are also significant (e.g., brain artery analysis). This paper explores a combination of data reduction and data partitioning to compute persistent homology on big data that enables the identification of both large and small topological features from the input data set. To reduce the approximation errors that typically accompany data reduction for persistent homology, the described method also includes a mechanism of ``upscaling'' the data circumscribing the large topological features that are computed from the sampled data. The designed experimental method provides significant results for improving the scale at which persistent homology can be performed 
    more » « less
  5. ; ; (, International Workshop on Big Data Reduction)
    An emerging method for data analysis is called Topological Data Analysis (TDA). TDA is based in the mathematical field of topology and examines the properties of spaces under continuous deformation. One of the key tools used for TDA is called persistent homology which considers the connectivity of points in a d-dimensional point cloud at different spatial resolutions to identify topological properties (holes, loops, and voids) in the space. Persistent homology then classifies the topological features by their persistence through the range of spatial connectivity. Unfortunately the memory and run-time complexity of computing persistent homology is exponential and current tools can only process a few thousand points in R3. Fortunately, the use of data reduction techniques enables persistent homology to be applied to much larger point clouds. Techniques to reduce the data range from random sampling of points to clustering the data and using the cluster centroids as the reduced data. While several data reduction approaches appear to preserve the large topological features present in the original point cloud, no systematic study comparing the efficacy of different data clustering techniques in preserving the persistent homology results has been performed. This paper explores the question of topology preserving data reductions and describes formally when and how topological features can be mischaracterized or lost by data reduction techniques. The paper also performs an experimental assessment of data reduction techniques and resilient effects on the persistent homology. In particular, data reduction by random selection is compared to cluster centroids extracted from different data clustering algorithms. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email