CASSCF response equations revisited: a simple and efficient iterative algorithm

We present an algorithm to solve the CASSCF linear response equations that is both simple and efficient. The algorithm makes use of the well established symmetric and antisymmetric combinations of trial vectors, but further orthogonalizes them with respect to the scalar product induced by the response matrix. This leads to a standard, symmetric, block eigenvalue problem in the expansion subspace that can be solved by diagonalizing a symmetric, positive definite matrix half the size of the expansion space. Preliminary numerical tests show that the algorithm is robust and stable

A robust, open-source implementation of the locally optimal block preconditioned conjugate gradient for large eigenvalue problems in quantum chemistry

We present two open-source implementations of the Locally Optimal Block Preconditioned Conjugate Gradient (LOBPCG) algorithm to find a few eigenvalues and eigenvectors of large, possibly sparse matrices. We then test LOBPCG for various quantum chemistry problems, encompassing medium to large, dense to sparse, wellbehaved to ill-conditioned ones, where the standard method typically used is Davidson's diagonalization. Numerical tests show that, while Davidson's method remains the best choice for most applications in quantum chemistry, LOBPCG represents a competitive alternative, especially when memory is an issue, and can even outperform Davidson for ill-conditioned, non diagonally dominant problems.Comment: Theoretical Chemistry Accounts: Theory, Computation, and Modeling, In pres

Antitumor activity of the retinoid-related molecules (E)-3-(4â\u80²- hydroxy-3â\u80²-adamantylbiphenyl-4-yl)acrylic acid (ST1926) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) in F9 teratocarcinoma: Role of retinoic acid receptor γ and retinoid-independent pathways

International audienceThe retinoid-related molecules (RRMs) ST1926 [(E)-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid] and CD437 (6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid) are promising anticancer agents. We compared the retinoic acid receptor (RAR) trans-activating properties of the two RRMs and all-trans-retinoic acid (ATRA). ST1926 and CD437 are better RARgamma agonists than ATRA. We used three teratocarcinoma cell lines to evaluate the significance of RARgamma in the activity of RRMs: F9-wild type (WT); F9gamma-/-, lacking the RARgamma gene; F9gamma51, aF9gamma-/-derivative, complemented for the RARgamma deficit. Similar to ATRA, ST1926 and CD437 activate cytodifferentiation only in F9-WT cells. Unlike ATRA, ST1926 and CD437 arrest cells in the G2/M phase of the cell cycle and induce apoptosis in all F9 cell lines. Our data indicate that RARgamma and the classic retinoid pathway are not relevant for the antiproliferative and apoptotic activities of RRMs in vitro. Increases in cytosolic calcium are fundamental for apoptosis, in that intracellular calcium chelators abrogate the process. Comparison of the gene expression profiles associated with ST1926 and ATRA in F9-WT and F9gamma-/-indicates that the RRM activates a conspicuous nonretinoid response in addition to the classic and RAR-dependent pathway. The pattern of genes regulated by ST1926 selectively, in a RARgamma-independent manner, provides novel insights into the possible molecular determinants underlying the activity of RRMs in vitro. Furthermore, it suggests that RARgamma-dependent responses are relevant to the activity of RRMs in vivo. Indeed, the receptor hinders the antitumor activity in vivo, in that both syngeneic and immunosuppressed SCID mice bearing F9gamma-/- tumors have increased life spans after treatment with ST1926 and CD437 relative to their F9-WT counterparts

P38MAPK-dependent phosphorylation and degradation of SRC-3/AIB1 and RARα-mediated transcription

Nuclear retinoic acid (RA) receptors (RARs) activate gene expression through dynamic interactions with coregulators in coordination with the ligand and phosphorylation processes. Here we show that during RA-dependent activation of the RARα isotype, the p160 coactivator pCIP/ACTR/AIB-1/RAC-3/TRAM-1/SRC-3 is phosphorylated by p38MAPK. SRC-3 phosphorylation has been correlated to an initial facilitation of RARα-target genes activation, via the control of the dynamics of the interactions of the coactivator with RARα. Then, phosphorylation inhibits transcription via promoting the degradation of SRC-3. In line with this, inhibition of p38MAPK markedly enhances RARα-mediated transcription and RA-dependent induction of cell differentiation. SRC-3 phosphorylation and degradation occur only within the context of RARα complexes, suggesting that the RAR isotype defines a phosphorylation code through dictating the accessibility of the coactivator to p38MAPK. We propose a model in which RARα transcriptional activity is regulated by SRC-3 through coordinated events that are fine-tuned by RA and p38MAPK