DOGS: Reaction-Driven de novo Design of Bioactive Compounds

We present a computational method for the reaction-based de novo design of drug-like molecules. The software DOGS (Design of Genuine Structures) features a ligand-based strategy for automated ‘in silico’ assembly of potentially novel bioactive compounds. The quality of the designed compounds is assessed by a graph kernel method measuring their similarity to known bioactive reference ligands in terms of structural and pharmacophoric features. We implemented a deterministic compound construction procedure that explicitly considers compound synthesizability, based on a compilation of 25'144 readily available synthetic building blocks and 58 established reaction principles. This enables the software to suggest a synthesis route for each designed compound. Two prospective case studies are presented together with details on the algorithm and its implementation. De novo designed ligand candidates for the human histamine H4 receptor and γ-secretase were synthesized as suggested by the software. The computational approach proved to be suitable for scaffold-hopping from known ligands to novel chemotypes, and for generating bioactive molecules with drug-like properties

Sovereign credit ratings, emerging market risk and financial market volatility

SIGLEAvailable from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel W 706 (55) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Boom and Bust and Sovereign Ratings

The 1990s have witnessed pronounced boom-bust cycles in emerging-markets lending, culminating in the Asian financial and currency crisis of 1997-98. By examining the links between sovereign credit ratings and dollar bond yield spreads over 1989-97, this paper aims at broad empirical content for judging whether the three leading rating agencies — Moody’s, Standard ' Poor’s and Fitch IBCA — can intensify or attenuate boom-bust cycles in emerging-market lending. First, an event study exploring the market response for 30 trading days before and after rating announcements finds a significant impact of imminent upgrades and implemented downgrades for a combination of ratings by the three leading agencies, despite strong anticipation of rating events. Second, a Granger causality test, by correcting for joint determinants of ratings and yield spreads, finds that changes in sovereign ratings are mutually interdependent with changes in bond yields. These findings are based on many more ... Les années 90 ont été marquées par une succession de cycles d’expansion-contraction de grande ampleur dans les opérations de prêts destinés aux marchés émergents. Cette volatilité a culminé avec la crise monétaire et financière qui a atteint l’Asie en 1997-98. La relation entre les notations de crédit souverain et les écarts de rendement des obligations en dollar sur la période 1989-97 est examinée dans ce document. Sur la base de ces données empiriques, les auteurs visent à évaluer si les trois principales agences de notation — Moody’s, Standard ' Poor’s et Fitch IBCA — amplifient ou atténuent les cycles d’expansion-contraction des opérations de prêt sur les marchés émergents. En premier lieu, la réponse du marché avant et après la diffusion des notations est étudiée sur 30 jours ouvrables. Il en ressort que, en dépit d’une anticipation élevée des annonces, l’impact des hausses pressenties et des notations à la baisse est important, pour une combinaison des cotes des trois agences ...credit rating, emerging markets, currency crisis, sovereign risk

Emerging Market Risk and Sovereign Credit Ratings

In principle, the sovereign credit rating industry could help mitigate the congestion externalities common to world capital markets that arise from the failure of market participants to internalise the social cost of external borrowings. This would require that modifications in ratings on government bonds convey new information to market participants, with changes in credit ratings leading to changes in country risk premia. Using panel data analysis and event studies this paper presents econometric evidence that changes in credit rating have a significant impact on international financial markets. In line with earlier studies, our event study finds a highly significant announcement effect when emerging-market sovereign bonds are put on review with negative outlook. Our findings imply that the sovereign rating industry has the potential to help dampen excessive private capital inflows into the emerging markets with negative rating announcements ... En principe, l’existence d’agences d’évaluation financière ( the sovereign credit rating industry ) pourrait contribuer à limiter les externalités dues à l’afflux de capitaux étrangers et communes à tous les marchés des capitaux du fait de l’incapacité des acteurs du marché à internaliser le coût social des emprunts extérieurs. Toute nouvelle cotation des obligations d’État devrait transmettre de nouvelles informations aux intervenants sur le marché et les changements dans les évaluations financières devraient se répercuter sur l’évolution du risque pays. Ce document technique repose sur une analyse en données de panel et sur des études de cas ; il ressort de l’analyse économétrique que les changements dans les cotations ont des répercussions importantes sur les marchés financiers internationaux. Notre analyse, qui s’inscrit dans le prolongement des travaux précédents, met en évidence un effet d’annonce très significatif quand les perspectives d’évolution des obligations d’État sur ...